Signaling by FGFR1 (Homo sapiens)

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1. Smedley D, Demiroglu A, Abdul-Rauf M, Heath C, Cooper C, Shipley J, Cross NC.; ''ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.''; PubMed Europe PMC Scholia
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3. Greulich H, Pollock PM.; ''Targeting mutant fibroblast growth factor receptors in cancer.''; PubMed Europe PMC Scholia
4. Chase A, Grand FH, Cross NC.; ''Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome.''; PubMed Europe PMC Scholia
5. Hall AB, Jura N, DaSilva J, Jang YJ, Gong D, Bar-Sagi D.; ''hSpry2 is targeted to the ubiquitin-dependent proteasome pathway by c-Cbl.''; PubMed Europe PMC Scholia
6. Ong SH, Guy GR, Hadari YR, Laks S, Gotoh N, Schlessinger J, Lax I.; ''FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors.''; PubMed Europe PMC Scholia
7. Trueb B, Amann R, Gerber SD.; ''Role of FGFRL1 and other FGF signaling proteins in early kidney development.''; PubMed Europe PMC Scholia
8. Petiot A, Ferretti P, Copp AJ, Chan CT.; ''Induction of chondrogenesis in neural crest cells by mutant fibroblast growth factor receptors.''; PubMed Europe PMC Scholia
9. Dutt A, Salvesen HB, Chen TH, Ramos AH, Onofrio RC, Hatton C, Nicoletti R, Winckler W, Grewal R, Hanna M, Wyhs N, Ziaugra L, Richter DJ, Trovik J, Engelsen IB, Stefansson IM, Fennell T, Cibulskis K, Zody MC, Akslen LA, Gabriel S, Wong KK, Sellers WR, Meyerson M, Greulich H.; ''Drug-sensitive FGFR2 mutations in endometrial carcinoma.''; PubMed Europe PMC Scholia
10. Gartside MG, Chen H, Ibrahimi OA, Byron SA, Curtis AV, Wellens CL, Bengston A, Yudt LM, Eliseenkova AV, Ma J, Curtin JA, Hyder P, Harper UL, Riedesel E, Mann GJ, Trent JM, Bastian BC, Meltzer PS, Mohammadi M, Pollock PM.; ''Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma.''; PubMed Europe PMC Scholia
11. Yu K, Herr AB, Waksman G, Ornitz DM.; ''Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome.''; PubMed Europe PMC Scholia
12. Popovici C, Zhang B, Grégoire MJ, Jonveaux P, Lafage-Pochitaloff M, Birnbaum D, Pébusque MJ.; ''The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1.''; PubMed Europe PMC Scholia
13. Cargnello M, Roux PP.; ''Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.''; PubMed Europe PMC Scholia
14. Gerber SD, Steinberg F, Beyeler M, Villiger PM, Trueb B.; ''The murine Fgfrl1 receptor is essential for the development of the metanephric kidney.''; PubMed Europe PMC Scholia
15. Demiroglu A, Steer EJ, Heath C, Taylor K, Bentley M, Allen SL, Koduru P, Brody JP, Hawson G, Rodwell R, Doody ML, Carnicero F, Reiter A, Goldman JM, Melo JV, Cross NC.; ''The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins.''; PubMed Europe PMC Scholia
16. Dodé C, Hardelin JP.; ''Kallmann syndrome.''; PubMed Europe PMC Scholia
17. Zhen Y, Sørensen V, Jin Y, Suo Z, Wiedłocha A.; ''Indirubin-3'-monoxime inhibits autophosphorylation of FGFR1 and stimulates ERK1/2 activity via p38 MAPK.''; PubMed Europe PMC Scholia
18. Ollendorff V, Guasch G, Isnardon D, Galindo R, Birnbaum D, Pébusque MJ.; ''Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation.''; PubMed Europe PMC Scholia
19. Hu Y, Bouloux PM.; ''Novel insights in FGFR1 regulation: lessons from Kallmann syndrome.''; PubMed Europe PMC Scholia
20. Williams EJ, Furness J, Walsh FS, Doherty P.; ''Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin.''; PubMed Europe PMC Scholia
21. Popovici C, Adélaïde J, Ollendorff V, Chaffanet M, Guasch G, Jacrot M, Leroux D, Birnbaum D, Pébusque MJ.; ''Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13).''; PubMed Europe PMC Scholia
22. Brown MD, Sacks DB.; ''Protein scaffolds in MAP kinase signalling.''; PubMed Europe PMC Scholia
23. Lim J, Yusoff P, Wong ES, Chandramouli S, Lao DH, Fong CW, Guy GR.; ''The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes.''; PubMed Europe PMC Scholia
24. Robertson A, MacColl GS, Nash JA, Boehm MK, Perkins SJ, Bouloux PM.; ''Molecular modelling and experimental studies of mutation and cell-adhesion sites in the fibronectin type III and whey acidic protein domains of human anosmin-1.''; PubMed Europe PMC Scholia
25. Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
26. Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM.; ''Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family.''; PubMed Europe PMC Scholia
27. Cross MJ, Hodgkin MN, Roberts S, Landgren E, Wakelam MJ, Claesson-Welsh L.; ''Tyrosine 766 in the fibroblast growth factor receptor-1 is required for FGF-stimulation of phospholipase C, phospholipase D, phospholipase A(2), phosphoinositide 3-kinase and cytoskeletal reorganisation in porcine aortic endothelial cells.''; PubMed Europe PMC Scholia
28. Tavormina PL, Bellus GA, Webster MK, Bamshad MJ, Fraley AE, McIntosh I, Szabo J, Jiang W, Jiang W, Jabs EW, Wilcox WR, Wasmuth JJ, Donoghue DJ, Thompson LM, Francomano CA.; ''A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene.''; PubMed Europe PMC Scholia
29. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T.; ''Klotho converts canonical FGF receptor into a specific receptor for FGF23.''; PubMed Europe PMC Scholia
30. Rubin C, Litvak V, Medvedovsky H, Zwang Y, Lev S, Yarden Y.; ''Sprouty fine-tunes EGF signaling through interlinked positive and negative feedback loops.''; PubMed Europe PMC Scholia
31. Guasch G, Mack GJ, Popovici C, Dastugue N, Birnbaum D, Rattner JB, Pébusque MJ.; ''FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).''; PubMed Europe PMC Scholia
32. Roskoski R.; ''ERK1/2 MAP kinases: structure, function, and regulation.''; PubMed Europe PMC Scholia
33. Muenke M, Schell U, Hehr A, Robin NH, Losken HW, Schinzel A, Pulleyn LJ, Rutland P, Reardon W, Malcolm S.; ''A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome.''; PubMed Europe PMC Scholia
34. Wu Y, Chen Z, Ullrich A.; ''EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2.''; PubMed Europe PMC Scholia
35. Gotoh N.; ''Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins.''; PubMed Europe PMC Scholia
36. Chen J, Deangelo DJ, Kutok JL, Williams IR, Lee BH, Wadleigh M, Duclos N, Cohen S, Adelsperger J, Okabe R, Coburn A, Galinsky I, Huntly B, Cohen PS, Meyer T, Fabbro D, Roesel J, Banerji L, Griffin JD, Xiao S, Fletcher JA, Stone RM, Gilliland DG.; ''PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder.''; PubMed Europe PMC Scholia
37. Wang R, Wang L, Li Y, Hu H, Shen L, Shen X, Pan Y, Ye T, Zhang Y, Luo X, Zhang Y, Pan B, Li B, Li H, Zhang J, Pao W, Ji H, Sun Y, Chen H.; ''FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer.''; PubMed Europe PMC Scholia
38. Soler G, Nusbaum S, Varet B, Macintyre EA, Vekemans M, Romana SP, Radford-Weiss I.; ''LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome.''; PubMed Europe PMC Scholia
39. Hidalgo-Curtis C, Chase A, Drachenberg M, Roberts MW, Finkelstein JZ, Mould S, Oscier D, Cross NC, Grand FH.; ''The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1.''; PubMed Europe PMC Scholia
40. Harkiolaki M, Tsirka T, Lewitzky M, Simister PC, Joshi D, Bird LE, Jones EY, O'Reilly N, Feller SM.; ''Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2.''; PubMed Europe PMC Scholia
41. Eswarakumar VP, Lax I, Schlessinger J.; ''Cellular signaling by fibroblast growth factor receptors.''; PubMed Europe PMC Scholia
42. Simon R, Richter J, Wagner U, Fijan A, Bruderer J, Schmid U, Ackermann D, Maurer R, Alund G, Knönagel H, Rist M, Wilber K, Anabitarte M, Hering F, Hardmeier T, Schönenberger A, Flury R, Jäger P, Fehr JL, Schraml P, Moch H, Mihatsch MJ, Gasser T, Sauter G.; ''High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer.''; PubMed Europe PMC Scholia
43. Lao DH, Yusoff P, Chandramouli S, Philp RJ, Fong CW, Jackson RA, Saw TY, Yu CY, Guy GR.; ''Direct binding of PP2A to Sprouty2 and phosphorylation changes are a prerequisite for ERK inhibition downstream of fibroblast growth factor receptor stimulation.''; PubMed Europe PMC Scholia
44. Gotoh N, Laks S, Nakashima M, Lax I, Schlessinger J.; ''FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts.''; PubMed Europe PMC Scholia
45. Jacquemier J, Adelaide J, Parc P, Penault-Llorca F, Planche J, deLapeyriere O, Birnbaum D.; ''Expression of the FGFR1 gene in human breast-carcinoma cells.''; PubMed Europe PMC Scholia
46. Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J.; ''Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.''; PubMed Europe PMC Scholia
47. Guasch G, Ollendorff V, Borg JP, Birnbaum D, Pébusque MJ.; ''8p12 stem cell myeloproliferative disorder: the FOP-fibroblast growth factor receptor 1 fusion protein of the t(6;8) translocation induces cell survival mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt/mTOR pathways.''; PubMed Europe PMC Scholia
48. Hart KC, Robertson SC, Donoghue DJ.; ''Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, Stat activation, and phosphatidylinositol 3-kinase activation.''; PubMed Europe PMC Scholia
49. Ong SH, Goh KC, Lim YP, Low BC, Klint P, Claesson-Welsh L, Cao X, Tan YH, Guy GR.; ''Suc1-associated neurotrophic factor target (SNT) protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2.''; PubMed Europe PMC Scholia
50. Koziczak M, Holbro T, Hynes NE.; ''Blocking of FGFR signaling inhibits breast cancer cell proliferation through downregulation of D-type cyclins.''; PubMed Europe PMC Scholia
51. Mohi MG, Neel BG.; ''The role of Shp2 (PTPN11) in cancer.''; PubMed Europe PMC Scholia
52. Chardin P, Camonis JH, Gale NW, van Aelst L, Schlessinger J, Wigler MH, Bar-Sagi D.; ''Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.''; PubMed Europe PMC Scholia
53. Silva PN, Altamentova SM, Kilkenny DM, Rocheleau JV.; ''Fibroblast growth factor receptor like-1 (FGFRL1) interacts with SHP-1 phosphatase at insulin secretory granules and induces beta-cell ERK1/2 protein activation.''; PubMed Europe PMC Scholia
54. Lelièvre H, Chevrier V, Tassin AM, Birnbaum D.; ''Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cgamma at the centrosome.''; PubMed Europe PMC Scholia
55. DaSilva J, Xu L, Kim HJ, Miller WT, Bar-Sagi D.; ''Regulation of sprouty stability by Mnk1-dependent phosphorylation.''; PubMed Europe PMC Scholia
56. Schüller AC, Ahmed Z, Levitt JA, Suen KM, Suhling K, Ladbury JE.; ''Indirect recruitment of the signalling adaptor Shc to the fibroblast growth factor receptor 2 (FGFR2).''; PubMed Europe PMC Scholia
57. Sleeman M, Fraser J, McDonald M, Yuan S, White D, Grandison P, Kumble K, Watson JD, Murison JG.; ''Identification of a new fibroblast growth factor receptor, FGFR5.''; PubMed Europe PMC Scholia
58. McClatchey AI, Cichowski K.; ''SPRED proteins provide a NF-ty link to Ras suppression.''; PubMed Europe PMC Scholia
59. Hu Y, González-Martínez D, Kim SH, Bouloux PM.; ''Cross-talk of anosmin-1, the protein implicated in X-linked Kallmann's syndrome, with heparan sulphate and urokinase-type plasminogen activator.''; PubMed Europe PMC Scholia
60. Ibrahimi OA, Zhang F, Eliseenkova AV, Linhardt RJ, Mohammadi M.; ''Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity.''; PubMed Europe PMC Scholia
61. Haines BP, Wheldon LM, Summerbell D, Heath JK, Rigby PW.; ''Regulated expression of FLRT genes implies a functional role in the regulation of FGF signalling during mouse development.''; PubMed Europe PMC Scholia
62. Lao DH, Chandramouli S, Yusoff P, Fong CW, Saw TY, Tai LP, Yu CY, Leong HF, Guy GR.; ''A Src homology 3-binding sequence on the C terminus of Sprouty2 is necessary for inhibition of the Ras/ERK pathway downstream of fibroblast growth factor receptor stimulation.''; PubMed Europe PMC Scholia
63. Roberts PJ, Der CJ.; ''Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.''; PubMed Europe PMC Scholia
64. Xiao S, McCarthy JG, Aster JC, Fletcher JA.; ''ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain.''; PubMed Europe PMC Scholia
65. Missiaglia E, Selfe J, Hamdi M, Williamson D, Schaaf G, Fang C, Koster J, Summersgill B, Messahel B, Versteeg R, Pritchard-Jones K, Kool M, Shipley J.; ''Genomic imbalances in rhabdomyosarcoma cell lines affect expression of genes frequently altered in primary tumors: an approach to identify candidate genes involved in tumor development.''; PubMed Europe PMC Scholia
66. Cha JY, Lambert QT, Reuther GW, Der CJ.; ''Involvement of fibroblast growth factor receptor 2 isoform switching in mammary oncogenesis.''; PubMed Europe PMC Scholia
67. McKay MM, Morrison DK.; ''Integrating signals from RTKs to ERK/MAPK.''; PubMed Europe PMC Scholia
68. Roumiantsev S, Krause DS, Neumann CA, Dimitri CA, Asiedu F, Cross NC, Van Etten RA.; ''Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations.''; PubMed Europe PMC Scholia
69. Knights V, Cook SJ.; ''De-regulated FGF receptors as therapeutic targets in cancer.''; PubMed Europe PMC Scholia
70. Hadari YR, Gotoh N, Kouhara H, Lax I, Schlessinger J.; ''Critical role for the docking-protein FRS2 alpha in FGF receptor-mediated signal transduction pathways.''; PubMed Europe PMC Scholia
71. Rubin C, Zwang Y, Vaisman N, Ron D, Yarden Y.; ''Phosphorylation of carboxyl-terminal tyrosines modulates the specificity of Sprouty-2 inhibition of different signaling pathways.''; PubMed Europe PMC Scholia
72. Rand V, Huang J, Stockwell T, Ferriera S, Buzko O, Levy S, Busam D, Li K, Edwards JB, Eberhart C, Murphy KM, Tsiamouri A, Beeson K, Simpson AJ, Venter JC, Riggins GJ, Strausberg RL.; ''Sequence survey of receptor tyrosine kinases reveals mutations in glioblastomas.''; PubMed Europe PMC Scholia
73. Ahmed Z, Schüller AC, Suhling K, Tregidgo C, Ladbury JE.; ''Extracellular point mutations in FGFR2 elicit unexpected changes in intracellular signalling.''; PubMed Europe PMC Scholia
74. Onishi-Haraikawa Y, Funaki M, Gotoh N, Shibuya M, Inukai K, Katagiri H, Fukushima Y, Anai M, Ogihara T, Sakoda H, Ono H, Kikuchi M, Oka Y, Asano T.; ''Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein.''; PubMed Europe PMC Scholia
75. Fukumoto T, Kubota Y, Kitanaka A, Yamaoka G, Ohara-Waki F, Imataki O, Ohnishi H, Ishida T, Tanaka T.; ''Gab1 transduces PI3K-mediated erythropoietin signals to the Erk pathway and regulates erythropoietin-dependent proliferation and survival of erythroid cells.''; PubMed Europe PMC Scholia
76. Wang JK, Gao G, Goldfarb M.; ''Fibroblast growth factor receptors have different signaling and mitogenic potentials.''; PubMed Europe PMC Scholia
77. Schlessinger J.; ''Common and distinct elements in cellular signaling via EGF and FGF receptors.''; PubMed Europe PMC Scholia
78. Wong ES, Lim J, Low BC, Chen Q, Guy GR.; ''Evidence for direct interaction between Sprouty and Cbl.''; PubMed Europe PMC Scholia
79. Dutt A, Ramos AH, Hammerman PS, Mermel C, Cho J, Sharifnia T, Chande A, Tanaka KE, Stransky N, Greulich H, Gray NS, Meyerson M.; ''Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer.''; PubMed Europe PMC Scholia
80. Pitteloud N, Meysing A, Quinton R, Acierno JS, Dwyer AA, Plummer L, Fliers E, Boepple P, Hayes F, Seminara S, Hughes VA, Ma J, Bouloux P, Mohammadi M, Crowley WF.; ''Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes.''; PubMed Europe PMC Scholia
81. González-Martínez D, Kim SH, Hu Y, Guimond S, Schofield J, Winyard P, Vannelli GB, Turnbull J, Bouloux PM.; ''Anosmin-1 modulates fibroblast growth factor receptor 1 signaling in human gonadotropin-releasing hormone olfactory neuroblasts through a heparan sulfate-dependent mechanism.''; PubMed Europe PMC Scholia
82. Raffioni S, Zhu YZ, Bradshaw RA, Thompson LM.; ''Effect of transmembrane and kinase domain mutations on fibroblast growth factor receptor 3 chimera signaling in PC12 cells. A model for the control of receptor tyrosine kinase activation.''; PubMed Europe PMC Scholia
83. Hart KC, Robertson SC, Kanemitsu MY, Meyer AN, Tynan JA, Donoghue DJ.; ''Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4.''; PubMed Europe PMC Scholia
84. Dailey L, Ambrosetti D, Mansukhani A, Basilico C.; ''Mechanisms underlying differential responses to FGF signaling.''; PubMed Europe PMC Scholia
85. Wheldon LM, Haines BP, Rajappa R, Mason I, Rigby PW, Heath JK.; ''Critical role of FLRT1 phosphorylation in the interdependent regulation of FLRT1 function and FGF receptor signalling.''; PubMed Europe PMC Scholia
86. di Martino E, L'Hôte CG, Kennedy W, Tomlinson DC, Knowles MA.; ''Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation-specific manner.''; PubMed Europe PMC Scholia
87. Kan SH, Elanko N, Johnson D, Cornejo-Roldan L, Cook J, Reich EW, Tomkins S, Verloes A, Twigg SR, Rannan-Eliya S, McDonald-McGinn DM, Zackai EH, Wall SA, Muenke M, Wilkie AO.; ''Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis.''; PubMed Europe PMC Scholia
88. Wesche J, Haglund K, Haugsten EM.; ''Fibroblast growth factors and their receptors in cancer.''; PubMed Europe PMC Scholia
89. Zhuang L, Villiger P, Trueb B.; ''Interaction of the receptor FGFRL1 with the negative regulator Spred1.''; PubMed Europe PMC Scholia
90. Belloni E, Trubia M, Gasparini P, Micucci C, Tapinassi C, Confalonieri S, Nuciforo P, Martino B, Lo-Coco F, Pelicci PG, Di Fiore PP.; ''8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes.''; PubMed Europe PMC Scholia
91. Zhou W, Feng X, Wu Y, Benge J, Zhang Z, Chen Z.; ''FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway.''; PubMed Europe PMC Scholia
92. Mohammadi M, Dionne CA, Li W, Li N, Spivak T, Honegger AM, Jaye M, Schlessinger J.; ''Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis.''; PubMed Europe PMC Scholia
93. Walz C, Chase A, Schoch C, Weisser A, Schlegel F, Hochhaus A, Fuchs R, Schmitt-Gräff A, Hehlmann R, Cross NC, Reiter A.; ''The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1.''; PubMed Europe PMC Scholia
94. Beenken A, Mohammadi M.; ''The FGF family: biology, pathophysiology and therapy.''; PubMed Europe PMC Scholia
95. Davies H, Hunter C, Smith R, Stephens P, Greenman C, Bignell G, Teague J, Butler A, Edkins S, Stevens C, Parker A, O'Meara S, Avis T, Barthorpe S, Brackenbury L, Buck G, Clements J, Cole J, Dicks E, Edwards K, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Shepherd R, Small A, Solomon H, Stephens Y, Tofts C, Varian J, Webb A, West S, Widaa S, Yates A, Brasseur F, Cooper CS, Flanagan AM, Green A, Knowles M, Leung SY, Looijenga LH, Malkowicz B, Pierotti MA, Teh BT, Yuen ST, Lakhani SR, Easton DF, Weber BL, Goldstraw P, Nicholson AG, Wooster R, Stratton MR, Futreal PA.; ''Somatic mutations of the protein kinase gene family in human lung cancer.''; PubMed Europe PMC Scholia
96. Cseh B, Doma E, Baccarini M.; ''"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.''; PubMed Europe PMC Scholia
97. Carpenter G, Ji Q.; ''Phospholipase C-gamma as a signal-transducing element.''; PubMed Europe PMC Scholia
98. Ornitz DM, Marie PJ.; ''FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease.''; PubMed Europe PMC Scholia
99. Turner N, Grose R.; ''Fibroblast growth factor signalling: from development to cancer.''; PubMed Europe PMC Scholia
100. Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schöttle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansén S, Rauh D, Baessmann I, Altmüller J, Wainer Z, Conron M, Wright G, Russell P, Solomon B, Brambilla E, Brambilla C, Lorimier P, Sollberg S, Brustugun OT, Engel-Riedel W, Ludwig C, Petersen I, Sänger J, Clement J, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman D, Cappuzzo F, Ligorio C, Damiani S, Hallek M, Beroukhim R, Pao W, Klebl B, Baumann M, Buettner R, Ernestus K, Stoelben E, Wolf J, Nürnberg P, Perner S, Thomas RK.; ''Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer.''; PubMed Europe PMC Scholia
101. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
102. Klint P, Kanda S, Claesson-Welsh L.; ''Shc and a novel 89-kDa component couple to the Grb2-Sos complex in fibroblast growth factor-2-stimulated cells.''; PubMed Europe PMC Scholia
103. Cancer Genome Atlas Research Network.; ''Comprehensive genomic characterization defines human glioblastoma genes and core pathways.''; PubMed Europe PMC Scholia
104. Minegishi Y, Iwanari H, Mochizuki Y, Horii T, Hoshino T, Kodama T, Hamakubo T, Gotoh N.; ''Prominent expression of FRS2beta protein in neural cells and its association with intracellular vesicles.''; PubMed Europe PMC Scholia
105. Pollock PM, Gartside MG, Dejeza LC, Powell MA, Mallon MA, Davies H, Mohammadi M, Futreal PA, Stratton MR, Trent JM, Goodfellow PJ.; ''Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes.''; PubMed Europe PMC Scholia
106. Li X, Brunton VG, Burgar HR, Wheldon LM, Heath JK.; ''FRS2-dependent SRC activation is required for fibroblast growth factor receptor-induced phosphorylation of Sprouty and suppression of ERK activity.''; PubMed Europe PMC Scholia
107. Wong A, Lamothe B, Lee A, Schlessinger J, Lax I.; ''FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl.''; PubMed Europe PMC Scholia
108. Mohammadi M, Olsen SK, Ibrahimi OA.; ''Structural basis for fibroblast growth factor receptor activation.''; PubMed Europe PMC Scholia
109. Rieckmann T, Kotevic I, Trueb B.; ''The cell surface receptor FGFRL1 forms constitutive dimers that promote cell adhesion.''; PubMed Europe PMC Scholia
110. Hu Y, Guimond SE, Travers P, Cadman S, Hohenester E, Turnbull JE, Kim SH, Bouloux PM.; ''Novel mechanisms of fibroblast growth factor receptor 1 regulation by extracellular matrix protein anosmin-1.''; PubMed Europe PMC Scholia
111. Lew ED, Furdui CM, Anderson KS, Schlessinger J.; ''The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations.''; PubMed Europe PMC Scholia
112. Impagnatiello MA, Weitzer S, Gannon G, Compagni A, Cotten M, Christofori G.; ''Mammalian sprouty-1 and -2 are membrane-anchored phosphoprotein inhibitors of growth factor signaling in endothelial cells.''; PubMed Europe PMC Scholia
113. Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R, Castano A, Liu EM, Reichel J, Porrati P, Pellegatta S, Qiu K, Gao Z, Ceccarelli M, Riccardi R, Brat DJ, Guha A, Aldape K, Golfinos JG, Zagzag D, Mikkelsen T, Finocchiaro G, Lasorella A, Rabadan R, Iavarone A.; ''Transforming fusions of FGFR and TACC genes in human glioblastoma.''; PubMed Europe PMC Scholia
114. Turner N, Pearson A, Sharpe R, Lambros M, Geyer F, Lopez-Garcia MA, Natrajan R, Marchio C, Iorns E, Mackay A, Gillett C, Grigoriadis A, Tutt A, Reis-Filho JS, Ashworth A.; ''FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer.''; PubMed Europe PMC Scholia
115. Steinberg F, Zhuang L, Beyeler M, Kälin RE, Mullis PE, Brändli AW, Trueb B.; ''The FGFRL1 receptor is shed from cell membranes, binds fibroblast growth factors (FGFs), and antagonizes FGF signaling in Xenopus embryos.''; PubMed Europe PMC Scholia
116. Böttcher RT, Pollet N, Delius H, Niehrs C.; ''The transmembrane protein XFLRT3 forms a complex with FGF receptors and promotes FGF signalling.''; PubMed Europe PMC Scholia
117. Yigzaw Y, Cartin L, Pierre S, Scholich K, Patel TB.; ''The C terminus of sprouty is important for modulation of cellular migration and proliferation.''; PubMed Europe PMC Scholia
118. Xu H, Lee KW, Goldfarb M.; ''Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins.''; PubMed Europe PMC Scholia
119. Wasag B, Lierman E, Meeus P, Cools J, Vandenberghe P.; ''The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11).''; PubMed Europe PMC Scholia
120. Ong SH, Lim YP, Low BC, Guy GR.; ''SHP2 associates directly with tyrosine phosphorylated p90 (SNT) protein in FGF-stimulated cells.''; PubMed Europe PMC Scholia
121. Kyriakis JM, Avruch J.; ''Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.''; PubMed Europe PMC Scholia
122. Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, Schlessinger J.; ''A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway.''; PubMed Europe PMC Scholia
123. Mohammadi M, Dikic I, Sorokin A, Burgess WH, Jaye M, Schlessinger J.; ''Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction.''; PubMed Europe PMC Scholia
124. Lim J, Wong ES, Ong SH, Yusoff P, Low BC, Guy GR.; ''Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain.''; PubMed Europe PMC Scholia
125. Chen J, Lee BH, Williams IR, Kutok JL, Mitsiades CS, Duclos N, Cohen S, Adelsperger J, Okabe R, Coburn A, Moore S, Huntly BJ, Fabbro D, Anderson KC, Griffin JD, Gilliland DG.; ''FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies.''; PubMed Europe PMC Scholia
126. Reiter A, Sohal J, Kulkarni S, Chase A, Macdonald DH, Aguiar RC, Gonçalves C, Hernandez JM, Jennings BA, Goldman JM, Cross NC.; ''Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome.''; PubMed Europe PMC Scholia
127. Gu TL, Goss VL, Reeves C, Popova L, Nardone J, Macneill J, Walters DK, Wang Y, Rush J, Comb MJ, Druker BJ, Polakiewicz RD.; ''Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia.''; PubMed Europe PMC Scholia
128. Hanafusa H, Torii S, Yasunaga T, Matsumoto K, Nishida E.; ''Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty.''; PubMed Europe PMC Scholia
129. Plotnikov A, Zehorai E, Procaccia S, Seger R.; ''The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.''; PubMed Europe PMC Scholia
130. Grand EK, Grand FH, Chase AJ, Ross FM, Corcoran MM, Oscier DG, Cross NC.; ''Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.''; PubMed Europe PMC Scholia
131. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA.; ''Mutations of the BRAF gene in human cancer.''; PubMed Europe PMC Scholia
132. Freier K, Schwaenen C, Sticht C, Flechtenmacher C, Mühling J, Hofele C, Radlwimmer B, Lichter P, Joos S.; ''Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC).''; PubMed Europe PMC Scholia
133. Brady SC, Coleman ML, Munro J, Feller SM, Morrice NA, Olson MF.; ''Sprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation.''; PubMed Europe PMC Scholia
134. Xiao S, Nalabolu SR, Aster JC, Ma J, Abruzzo L, Jaffe ES, Stone R, Weissman SM, Hudson TJ, Fletcher JA.; ''FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome.''; PubMed Europe PMC Scholia
135. Ruhe JE, Streit S, Hart S, Wong CH, Specht K, Knyazev P, Knyazeva T, Tay LS, Loo HL, Foo P, Wong W, Pok S, Lim SJ, Ong H, Luo M, Ho HK, Peng K, Lee TC, Bezler M, Mann C, Gaertner S, Hoefler H, Iacobelli S, Peter S, Tay A, Brenner S, Venkatesh B, Ullrich A.; ''Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines.''; PubMed Europe PMC Scholia
136. Gerber SD, Amann R, Wyder S, Trueb B.; ''Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling.''; PubMed Europe PMC Scholia
137. Smit L, de Vries-Smits AM, Bos JL, Borst J.; ''B cell antigen receptor stimulation induces formation of a Shc-Grb2 complex containing multiple tyrosine-phosphorylated proteins.''; PubMed Europe PMC Scholia
138. Mohammadi M, Honegger AM, Rotin D, Fischer R, Bellot F, Li W, Dionne CA, Jaye M, Rubinstein M, Schlessinger J.; ''A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1.''; PubMed Europe PMC Scholia
139. Parker BC, Engels M, Annala M, Zhang W.; ''Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum of solid tumours.''; PubMed Europe PMC Scholia
140. Wellbrock C, Karasarides M, Marais R.; ''The RAF proteins take centre stage.''; PubMed Europe PMC Scholia
141. Jackson CC, Medeiros LJ, Miranda RN.; ''8p11 myeloproliferative syndrome: a review.''; PubMed Europe PMC Scholia
142. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
143. Ong SH, Hadari YR, Gotoh N, Guy GR, Schlessinger J, Lax I.; ''Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins.''; PubMed Europe PMC Scholia
144. Dance M, Montagner A, Salles JP, Yart A, Raynal P.; ''The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway.''; PubMed Europe PMC Scholia
145. Turjanski AG, Vaqué JP, Gutkind JS.; ''MAP kinases and the control of nuclear events.''; PubMed Europe PMC Scholia
146. Furdui CM, Lew ED, Schlessinger J, Anderson KS.; ''Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction.''; PubMed Europe PMC Scholia
147. Curto M, Frankel P, Carrero A, Foster DA.; ''Novel recruitment of Shc, Grb2, and Sos by fibroblast growth factor receptor-1 in v-Src-transformed cells.''; PubMed Europe PMC Scholia
148. Gorringe KL, Jacobs S, Thompson ER, Sridhar A, Qiu W, Choong DY, Campbell IG.; ''High-resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications.''; PubMed Europe PMC Scholia
149. Patterson RL, van Rossum DB, Nikolaidis N, Gill DL, Snyder SH.; ''Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling.''; PubMed Europe PMC Scholia
150. Lemmon MA, Schlessinger J.; ''Cell signaling by receptor tyrosine kinases.''; PubMed Europe PMC Scholia
151. Fong CW, Leong HF, Wong ES, Lim J, Yusoff P, Guy GR.; ''Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function.''; PubMed Europe PMC Scholia
152. Oliveira LM, Seminara SB, Beranova M, Hayes FJ, Valkenburgh SB, Schipani E, Costa EM, Latronico AC, Crowley WF, Vallejo M.; ''The importance of autosomal genes in Kallmann syndrome: genotype-phenotype correlations and neuroendocrine characteristics.''; PubMed Europe PMC Scholia
153. Kanai M, Göke M, Tsunekawa S, Podolsky DK.; ''Signal transduction pathway of human fibroblast growth factor receptor 3. Identification of a novel 66-kDa phosphoprotein.''; PubMed Europe PMC Scholia
154. Amann R, Trueb B.; ''Evidence that the novel receptor FGFRL1 signals indirectly via FGFR1.''; PubMed Europe PMC Scholia
155. Ibrahimi OA, Zhang F, Eliseenkova AV, Itoh N, Linhardt RJ, Mohammadi M.; ''Biochemical analysis of pathogenic ligand-dependent FGFR2 mutations suggests distinct pathophysiological mechanisms for craniofacial and limb abnormalities.''; PubMed Europe PMC Scholia
156. Lax I, Wong A, Lamothe B, Lee A, Frost A, Hawes J, Schlessinger J.; ''The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors.''; PubMed Europe PMC Scholia
157. Hadari YR, Kouhara H, Lax I, Schlessinger J.; ''Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation.''; PubMed Europe PMC Scholia
158. Guasch G, Popovici C, Mugneret F, Chaffanet M, Pontarotti P, Birnbaum D, Pébusque MJ.; ''Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3).''; PubMed Europe PMC Scholia
159. Heath C, Cross NC.; ''Critical role of STAT5 activation in transformation mediated by ZNF198-FGFR1.''; PubMed Europe PMC Scholia
160. Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, Lonigro RJ, Vats P, Wang R, Lin SF, Cheng AJ, Kunju LP, Siddiqui J, Tomlins SA, Wyngaard P, Sadis S, Roychowdhury S, Hussain MH, Feng FY, Zalupski MM, Talpaz M, Pienta KJ, Rhodes DR, Robinson DR, Chinnaiyan AM.; ''Identification of targetable FGFR gene fusions in diverse cancers.''; PubMed Europe PMC Scholia
161. Mason JM, Morrison DJ, Bassit B, Dimri M, Band H, Licht JD, Gross I.; ''Tyrosine phosphorylation of Sprouty proteins regulates their ability to inhibit growth factor signaling: a dual feedback loop.''; PubMed Europe PMC Scholia
162. Dodé C, Levilliers J, Dupont JM, De Paepe A, Le Dû N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pêcheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP.; ''Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.''; PubMed Europe PMC Scholia
163. Agazie YM, Movilla N, Ischenko I, Hayman MJ.; ''The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3.''; PubMed Europe PMC Scholia
164. Sattler M, Mohi MG, Pride YB, Quinnan LR, Malouf NA, Podar K, Gesbert F, Iwasaki H, Li S, Van Etten RA, Gu H, Griffin JD, Neel BG.; ''Critical role for Gab2 in transformation by BCR/ABL.''; PubMed Europe PMC Scholia
165. Yusoff P, Lao DH, Ong SH, Wong ES, Lim J, Lo TL, Leong HF, Fong CW, Guy GR.; ''Sprouty2 inhibits the Ras/MAP kinase pathway by inhibiting the activation of Raf.''; PubMed Europe PMC Scholia
166. Reis-Filho JS, Simpson PT, Turner NC, Lambros MB, Jones C, Mackay A, Grigoriadis A, Sarrio D, Savage K, Dexter T, Iravani M, Fenwick K, Weber B, Hardisson D, Schmitt FC, Schmitt FC, Palacios J, Lakhani SR, Ashworth A.; ''FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas.''; PubMed Europe PMC Scholia
167. Hatch NE, Hudson M, Seto ML, Cunningham ML, Bothwell M.; ''Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F.''; PubMed Europe PMC Scholia

History

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Compare	Revision	Action	Time	User	Comment
	114733	view	16:21, 25 January 2021	ReactomeTeam	Reactome version 75
	113177	view	11:24, 2 November 2020	ReactomeTeam	Reactome version 74
	112405	view	15:34, 9 October 2020	ReactomeTeam	Reactome version 73
	101309	view	11:20, 1 November 2018	ReactomeTeam	reactome version 66
	100846	view	20:51, 31 October 2018	ReactomeTeam	reactome version 65
	100387	view	19:25, 31 October 2018	ReactomeTeam	reactome version 64
	99934	view	16:09, 31 October 2018	ReactomeTeam	reactome version 63
	99489	view	14:42, 31 October 2018	ReactomeTeam	reactome version 62 (2nd attempt)
	99141	view	12:40, 31 October 2018	ReactomeTeam	reactome version 62
	94044	view	13:53, 16 August 2017	ReactomeTeam	reactome version 61
	93669	view	11:30, 9 August 2017	ReactomeTeam	reactome version 61
	87126	view	18:45, 18 July 2016	Egonw	Ontology Term : 'signaling pathway' added !
	86792	view	09:26, 11 July 2016	ReactomeTeam	reactome version 56
	83306	view	10:43, 18 November 2015	ReactomeTeam	Version54
	81443	view	12:58, 21 August 2015	ReactomeTeam	New pathway

External references

DataNodes

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Name	Type	Database reference	Comment
ADP	Metabolite	CHEBI:16761 (ChEBI)
ATP	Metabolite	CHEBI:15422 (ChEBI)
AZ 2171	Metabolite	CHEBI:556867 (ChEBI)	A broad specificity ATP-competitive inhibitor of FGF-, VEGF-, PDGF- and KIT receptors that is in Phase I and II clinical trials for treatment of gastric, breast and endometrial cancers.
AZD4547	Metabolite	CHEBI:63453 (ChEBI)	AZD4547 (Astra Zeneca) is a pan-FGFR inhibitor in Phase I clinical trials for patients with advanced gastric cancer (NCT01457846) and for patient with advanced solid tumors with or without amplified FGFR1 or 2 (NCT00979134) and in Phase I/II trials for breast cancer patients with FGFR1 amplifications (NCT01202591).
Activated FGFR1 mutants:p-FRS2:GRB2:GAB1:PI3K	Complex	R-HSA-5655217 (Reactome)
Activated FGFR1 mutants:p-FRS2:GRB2:GAB1:PIK3R1	Complex	R-HSA-5655218 (Reactome)
Activated FGFR1:p-8T-FRS2	Complex	R-HSA-5654260 (Reactome)
Activated FGFR1:p-FRS2:GRB2:GAB1:PI3K	Complex	R-HSA-5654205 (Reactome)
Activated FGFR1:p-FRS2:GRB2:GAB1:PIK3R1	Complex	R-HSA-5654186 (Reactome)
Activated FGFR1:p-FRS2:GRB2:SOS1	Complex	R-HSA-5654264 (Reactome)
Activated FGFR1:p-FRS2:p-PTPN11:GRB2:GAB1:PI3K	Complex	R-HSA-5654188 (Reactome)
Activated FGFR1:p-FRS2:p-PTPN11:p-CBL:GRB2	Complex	R-HSA-5654267 (Reactome)
Activated FGFR1:p-FRS2:p-PTPN11	Complex	R-HSA-5654204 (Reactome)
Activated FGFR1:p-FRS2	Complex	R-HSA-5654200 (Reactome)
Activated FGFR1:p-FRS3	Complex	R-HSA-5654261 (Reactome)
Activated FGFR1:p-FRS:PTPN11	Complex	R-HSA-5654268 (Reactome)
Activated FGFR1:p-FRS:p-PTPN11	Complex	R-HSA-5654271 (Reactome)
Activated FGFR1:p-FRS	Complex	R-HSA-5654262 (Reactome)
Activated FGFR1:p-SHC1:GRB2:SOS1	Complex	R-HSA-5654275 (Reactome)
Activated FGFR1:p-SHC1	Complex	R-HSA-5654273 (Reactome)
Activated FGFR:p-FRS2:p-PTPN11:GRB2:GAB1:PIK3R1	Complex	R-HSA-5654185 (Reactome)
Activated overexpressed FGFR1b homodimer	Complex	R-HSA-1982038 (Reactome)
Activated overexpressed FGFR1c homodimer	Complex	R-HSA-1982036 (Reactome)
Activated FGFR1 P252X mutants	Complex	R-HSA-2050642 (Reactome)
Activated FGFR1 mutant dimers with enhanced kinase activity	Complex	R-HSA-2023432 (Reactome)
Activated FGFR1 mutants and fusion:p-PLCG1	Complex	R-HSA-1839062 (Reactome)
Activated FGFR1 mutants and fusions:PLCG1	Complex	R-HSA-1839061 (Reactome)
Activated FGFR1 mutants and fusions	Complex	R-HSA-5691527 (Reactome)
Activated FGFR1 mutants:FRS2	Complex	R-HSA-5655296 (Reactome)
Activated FGFR1 mutants:p-FRS2	Complex	R-HSA-5655216 (Reactome)
Activated FGFR1 mutants	Complex	R-HSA-5655215 (Reactome)
Activated FGFR1 fusion mutants		R-HSA-1839058 (Reactome)
Activated FGFR1 mutant dimers with enhanced kinase activity		R-HSA-2023432 (Reactome)
Activated FGFR1 mutants		R-HSA-5655215 (Reactome)
Activated FGFR1:FRS2	Complex	R-HSA-5654176 (Reactome)
Activated FGFR1:FRS3	Complex	R-HSA-5654255 (Reactome)
Activated FGFR1:SHC1	Complex	R-HSA-5654258 (Reactome)
Activated FGFR1	Complex	R-HSA-5654170 (Reactome)
Activated FGFR1b homodimer	Complex	R-HSA-190430 (Reactome)
Activated FGFR1c bound to FGF23:Klotho	Complex	R-HSA-500333 (Reactome)
Activated FGFR1c homodimer	Complex	R-HSA-190425 (Reactome)
Activated overexpressed FGFR1 homodimers		R-HSA-1982041 (Reactome)
BCR-FGFR1 fusion	Protein	P11274 (Uniprot-TrEMBL)
BCR-p-FGFR1 fusion mutant dimer	Complex	R-HSA-1838980 (Reactome)
BCR-p-FGFR1 fusion	Protein	P11274 (Uniprot-TrEMBL)
BGJ398	Metabolite	CHEBI:63451 (ChEBI)	A pan-FGFR ATP-competitive inhibitor that is in phase I clinical trials for advanced solid malignancies with amplification or activation of FGFR1 and 2 or activation of FGFR3 (NCT01004224).
BRAF	Protein	P15056 (Uniprot-TrEMBL)
BRAF	Protein	P15056 (Uniprot-TrEMBL)
Brivanib	Metabolite	CHEBI:443041 (ChEBI)	Brivanib, from Bristol Myers Squibb, is an FGFR and VEGFR inhibitor that has anti-angiogenic effects and that is in clinical trials for endometrial cancer (NCT00888173) (Huynh, 2008). No specific data pertaining to the activity of Brivanib against activated or amplified FGFRs is available, however.
Brivanib alaninate	Metabolite	CHEBI:270995 (ChEBI)	Brivanib alaninate is the pro-drug of brivanib, a VEGFR- and FGFR-tyrosine kinase inhibitor that is in Phase I clinical trials for metastatic solid tumors and in patients with endometrial cancer (NCT0088173). No specific data pertaining to the activity of Brivanib against activated or amplified FGFRs is available, however.
CBL	Protein	P22681 (Uniprot-TrEMBL)
CBL	Protein	P22681 (Uniprot-TrEMBL)
CNTRL-FGFR1 fusion	Protein	Q7Z7A1-3 (Uniprot-TrEMBL)
CNTRL-p-2Y-FGFR1 fusion	Protein	Q7Z7A1-3 (Uniprot-TrEMBL)
CPSF6-FGFR1 fusion	Protein	Q16630 (Uniprot-TrEMBL)
CPSF6-p-2Y-FGFR1 fusion	Protein	Q16630 (Uniprot-TrEMBL)
CUX1-FGFR1 fusion	Protein	P39880 (Uniprot-TrEMBL)
CUX1-p-2Y-FGFR1 fusion	Protein	P39880 (Uniprot-TrEMBL)
DAG and IP3 signaling	Pathway	R-HSA-1489509 (Reactome)	This pathway describes the generation of DAG and IP3 by the PLCgamma-mediated hydrolysis of PIP2 and the subsequent downstream signaling events.
Dovitinib	Metabolite	CHEBI:594834 (ChEBI)	A Novartis tyrosine kinase inhibitor with activity against multiple tyrosine kinase receptors including FGFRs, VEGFRs, PDGFRs, KIT, FLT3 and CSFR. TKI258 is in Phase II clinical trials for advanced breast cancer in patients with and without FGFR1 amplification (NCT00958971), for endometrial cancer with WT or activated FGFR2 mutants (NCT01379534), for relapsed myeloma with and without the t4:14 FGFR3 translocation/amplification (NCT01058434), and in bladder cancer in cases where archived material is available to check for correlation with FGFR3 mutation status (NCT00790426).
E3810	Metabolite	CHEBI:65138 (ChEBI)	E-3810 is a dual VEGFR and FGFR inhibitor that has anti-angiogenic and anti-tumorigenic effects in preclinical studies (Bello, 2011). It is in Phase I clinical trials for patients with solid tumors (NCT01283945).
FGF1	Protein	P05230 (Uniprot-TrEMBL)
FGF10	Protein	O15520 (Uniprot-TrEMBL)
FGF17-1	Protein	O60258-1 (Uniprot-TrEMBL)
FGF2(10-155)	Protein	P09038 (Uniprot-TrEMBL)
FGF20	Protein	Q9NP95 (Uniprot-TrEMBL)
FGF22	Protein	Q9HCT0 (Uniprot-TrEMBL)
FGF23 bound to Klotho and FGFR1c	Complex	R-HSA-190218 (Reactome)
FGF23(25-251)	Protein	Q9GZV9 (Uniprot-TrEMBL)
FGF3	Protein	P11487 (Uniprot-TrEMBL)
FGF4	Protein	P08620 (Uniprot-TrEMBL)
FGF5-1	Protein	P12034-1 (Uniprot-TrEMBL)
FGF6	Protein	P10767 (Uniprot-TrEMBL)
FGF8-1	Protein	P55075-1 (Uniprot-TrEMBL)
FGF9	Protein	P31371 (Uniprot-TrEMBL)
FGFR1 mutants:p-FRS2:GRB2:SOS1	Complex	R-HSA-5655328 (Reactome)
FGFR1 K656E	Protein	P11362 (Uniprot-TrEMBL)
FGFR1 N546K	Protein	P11362 (Uniprot-TrEMBL)	weak constitutive activation of ligand independent binding based on analogy of FGFR3 N540 mutation in hypochondroplasia (Rand 2005)
FGFR1 P252S	Protein	P11362 (Uniprot-TrEMBL)	thought to increase # hydrogen bonds, increase ligand affinity and ligand binding range (Ruhe 2007)
FGFR1 P252T	Protein	P11362 (Uniprot-TrEMBL)	thought to increase # hydrogen bonds, increase ligand affinity and ligand binding range (Ruhe 2007)
FGFR1 P252X mutant dimers bound to FGFs	Complex	R-HSA-2050638 (Reactome)
FGFR1 P252X mutants	Complex	R-HSA-2012029 (Reactome)
FGFR1 R576W	Protein	P11362 (Uniprot-TrEMBL)
FGFR1 fusion mutant dimers:TKIs	Complex	R-HSA-1839036 (Reactome)
FGFR1 fusion mutant dimers	Complex	R-HSA-1839026 (Reactome)
FGFR1 fusion mutants	Complex	R-HSA-1839029 (Reactome)
FGFR1 mutant dimers with enhanced kinase activity	Complex	R-HSA-2023433 (Reactome)
FGFR1 mutants with enhanced kinase activity	Complex	R-HSA-2012030 (Reactome)
FGFR1OP-FGFR1 fusion	Protein	O95684 (Uniprot-TrEMBL)
FGFR1OP-p-FGFR1 fusion mutant dimer	Complex	R-HSA-1838997 (Reactome)
FGFR1OP-p-FGFR1 fusion	Protein	O95684 (Uniprot-TrEMBL)
FGFR1OP2-FGFR1 fusion	Protein	Q9NVK5 (Uniprot-TrEMBL)
FGFR1OP2-p-2Y-FGFR1 fusion	Protein	Q9NVK5 (Uniprot-TrEMBL)
FGFR1b	Protein	P11362-19 (Uniprot-TrEMBL)	While the existence of a "b" isoform of fibroblast growth factor receptor 1 is well established and its biochemical and functional properties have been extensively characterized (e.g., Mohammadi et al. 2005; Zhang et al. 2006), its amino acid sequence is not represented in reference protein sequence databases, except as the 47-residue polypeptide (deposited in GenBank as accession AAB19502) first used by Johnson et al. (1991) to distinguish the "b" and "c" isoforms of the receptor.
FGFR1b homodimer bound to FGF	Complex	R-HSA-190226 (Reactome)
FGFR1b homodimer	Complex	R-HSA-190228 (Reactome)
FGFR1b-binding FGFs	Complex	R-HSA-189963 (Reactome)
FGFR1b		P11362-19 (Uniprot-TrEMBL)	While the existence of a "b" isoform of fibroblast growth factor receptor 1 is well established and its biochemical and functional properties have been extensively characterized (e.g., Mohammadi et al. 2005; Zhang et al. 2006), its amino acid sequence is not represented in reference protein sequence databases, except as the 47-residue polypeptide (deposited in GenBank as accession AAB19502) first used by Johnson et al. (1991) to distinguish the "b" and "c" isoforms of the receptor.
FGFR1c	Protein	P11362-1 (Uniprot-TrEMBL)
FGFR1c P252R	Protein	P11362-1 (Uniprot-TrEMBL)
FGFR1c homodimer bound to FGF	Complex	R-HSA-190233 (Reactome)
FGFR1c homodimer	Complex	R-HSA-190222 (Reactome)
FGFR1c-binding FGFs	Complex	R-HSA-189953 (Reactome)
FGFR1c:KAL1	Complex	R-HSA-5654346 (Reactome)
FGFR1c	Protein	P11362-1 (Uniprot-TrEMBL)
FRS2	Protein	Q8WU20 (Uniprot-TrEMBL)
FRS2	Protein	Q8WU20 (Uniprot-TrEMBL)
FRS3	Protein	O43559 (Uniprot-TrEMBL)
FRS3	Protein	O43559 (Uniprot-TrEMBL)
GAB1	Protein	Q13480 (Uniprot-TrEMBL)
GAB2	Protein	Q9UQC2 (Uniprot-TrEMBL)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GRB2-1	Protein	P62993-1 (Uniprot-TrEMBL)
GRB2-1:SOS1	Complex	R-HSA-109797 (Reactome)
GRB2-1	Protein	P62993-1 (Uniprot-TrEMBL)
GRB2:GAB1:PIK3R1	Complex	R-HSA-179864 (Reactome)
GRB2:GAB1	Complex	R-HSA-179849 (Reactome)
GRB2:GAB2	Complex	R-HSA-912522 (Reactome)
GTP	Metabolite	CHEBI:15996 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
HRAS	Protein	P01112 (Uniprot-TrEMBL)
HS	Metabolite	CHEBI:28815 (ChEBI)
HS	Metabolite	CHEBI:28815 (ChEBI)
IL17RD-1	Protein	Q8NFM7-1 (Uniprot-TrEMBL)
IL17RD-1	Protein	Q8NFM7-1 (Uniprot-TrEMBL)
IL17RD-4	Protein	Q8NFM7-4 (Uniprot-TrEMBL)
IL17RD	Complex	R-HSA-1268209 (Reactome)
KAL1	Protein	P23352 (Uniprot-TrEMBL)
KAL1:HS	Complex	R-HSA-5654355 (Reactome)
KL-1	Protein	Q9UEF7-1 (Uniprot-TrEMBL)
KL-2	Protein	Q9UEF7-2 (Uniprot-TrEMBL)
KRAS	Protein	P01116 (Uniprot-TrEMBL)
Klotho bound to FGF23	Complex	R-HSA-190208 (Reactome)
LRRFIP1-FGFR1 fusion	Protein	Q32MZ4 (Uniprot-TrEMBL)
LRRFIP1-p-2Y-FGFR1 fusion	Protein	Q32MZ4 (Uniprot-TrEMBL)
MAPK1	Protein	P28482 (Uniprot-TrEMBL)
MAPK3	Protein	P27361 (Uniprot-TrEMBL)
MYO18A-FGFR1 fusion	Protein	Q92614 (Uniprot-TrEMBL)
MYO18A-p-2Y-FGFR1 fusion	Protein	Q92614 (Uniprot-TrEMBL)
Midostaurin	Metabolite	CHEBI:63452 (ChEBI)	PKC412 is a multi-tyrosine kinase inhibitor that has been shown to be active against FGFR1 fusion proteins (Wasag, 2011; Chen,2004) and against multiple myeloma (Chen, 2005).
NRAS	Protein	P01111 (Uniprot-TrEMBL)
Overexpressed FGFR1:TKIs	Complex	R-HSA-2023442 (Reactome)
Overexpressed FGFR1 homodimers	Complex	R-HSA-1982053 (Reactome)
PD173074	Metabolite	CHEBI:63448 (ChEBI)	PD173074 is potent pan-FGFR reversible inhibitor that interacts with residues in the ATP-binding pocket and inhibits tyrosine kinase activity and autophosphorylation (Mohammadi, 1998; Ezzat, 2005). PD173074 is not suitable for therapeutic use due to issues with toxicity.
PI(3,4,5)P3	Metabolite	CHEBI:16618 (ChEBI)
PI(3,4,5)P3	Metabolite	CHEBI:16618 (ChEBI)
PI(4,5)P2	Metabolite	CHEBI:18348 (ChEBI)
PIK3CA	Protein	P42336 (Uniprot-TrEMBL)
PIK3CA	Protein	P42336 (Uniprot-TrEMBL)
PIK3R1	Protein	P27986 (Uniprot-TrEMBL)
PIK3R1	Protein	P27986 (Uniprot-TrEMBL)
PIP3 activates AKT signaling	Pathway	R-HSA-1257604 (Reactome)	Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007.
PLCG1	Protein	P19174 (Uniprot-TrEMBL)
PLCG1	Protein	P19174 (Uniprot-TrEMBL)
PP2A (A:C)	Complex	R-HSA-934544 (Reactome)
PP2A(A:C):S112/S121-pSPRY2	Complex	R-HSA-934578 (Reactome)
PP2A(A:C):SPRY2	Complex	R-HSA-934550 (Reactome)
PP2A(A:C):Y55/Y227-pSPRY2	Complex	R-HSA-934598 (Reactome)
PPA2A (A:C):S112/S115 p-SPRY2	Complex	R-HSA-1295605 (Reactome)
PPA2A (A:C):Y55/Y227 p-SPRY2:GRB2	Complex	R-HSA-1295625 (Reactome)
PPA2A(A:C):SPRY2	Complex	R-HSA-1295593 (Reactome)
PPP2CA	Protein	P67775 (Uniprot-TrEMBL)
PPP2CB	Protein	P62714 (Uniprot-TrEMBL)
PPP2R1A	Protein	P30153 (Uniprot-TrEMBL)
PTPN11	Protein	Q06124 (Uniprot-TrEMBL)
PTPN11	Protein	Q06124 (Uniprot-TrEMBL)
Phospho-MEK	Complex	R-HSA-169287 (Reactome)
Pi	Metabolite	CHEBI:18367 (ChEBI)
RAF/MAP kinase cascade	Pathway	R-HSA-5673001 (Reactome)	The RAS-RAF-MEK-ERK pathway regulates processes such as proliferation, differentiation, survival, senescence and cell motility in response to growth factors, hormones and cytokines, among others. Binding of these stimuli to receptors in the plasma membrane promotes the GEF-mediated activation of RAS at the plasma membrane and initiates the three-tiered kinase cascade of the conventional MAPK cascades. GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation (reviewed in Cseh et al, 2014; Roskoski, 2010; McKay and Morrison, 2007; Wellbrock et al, 2004). Activated RAF phosphorylates the MAPK kinase proteins MEK1 and MEK2 (also known as MAP2K1 and MAP2K2), which in turn phophorylate the proline-directed kinases ERK1 and 2 (also known as MAPK3 and MAPK1) (reviewed in Roskoski, 2012a, b; Kryiakis and Avruch, 2012). Activated ERK proteins may undergo dimerization and have identified targets in both the nucleus and the cytosol; consistent with this, a proportion of activated ERK protein relocalizes to the nucleus in response to stimuli (reviewed in Roskoski 2012b; Turjanski et al, 2007; Plotnikov et al, 2010; Cargnello et al, 2011). Although initially seen as a linear cascade originating at the plasma membrane and culminating in the nucleus, the RAS/RAF MAPK cascade is now also known to be activated from various intracellular location. Temporal and spatial specificity of the cascade is achieved in part through the interaction of pathway components with numerous scaffolding proteins (reviewed in McKay and Morrison, 2007; Brown and Sacks, 2009). The importance of the RAS/RAF MAPK cascade is highlighted by the fact that components of this pathway are mutated with high frequency in a large number of human cancers. Activating mutations in RAS are found in approximately one third of human cancers, while ~8% of tumors express an activated form of BRAF (Roberts and Der, 2007; Davies et al, 2002; Cantwell-Dorris et al, 2011).
RPS27A(1-76)	Protein	P62979 (Uniprot-TrEMBL)
S111/S120 p-SPRY2:B-RAF	Complex	R-HSA-1295587 (Reactome)
SHC1 p46,p52	Complex	R-HSA-1169480 (Reactome)	SHC1 isoforms p46 and p52 are found in B cells (Smit et al. 1994).
SHC1-2	Protein	P29353-2 (Uniprot-TrEMBL)
SHC1-3	Protein	P29353-3 (Uniprot-TrEMBL)
SOS1	Protein	Q07889 (Uniprot-TrEMBL)
SPRY2	Protein	O43597 (Uniprot-TrEMBL)
SPRY2:B-RAF	Complex	R-HSA-1295598 (Reactome)
SRC-1	Protein	P12931-1 (Uniprot-TrEMBL)
STAT1	Protein	P42224 (Uniprot-TrEMBL)
STAT1,3	Complex	R-HSA-1888196 (Reactome)
STAT3	Protein	P40763 (Uniprot-TrEMBL)
STAT5A	Protein	P42229 (Uniprot-TrEMBL)
STAT5B	Protein	P51692 (Uniprot-TrEMBL)
STAT5	Complex	R-HSA-452094 (Reactome)
SU5402	Metabolite	CHEBI:63449 (ChEBI)	SU5402 is an ATP-competitive FGFR and VEGFR inhibitor that is used as an in vitro reagent. Su5402 is not suitable for therapeutic use due to toxicity issues.
TRIM24-FGFR1 fusion	Protein	O15164 (Uniprot-TrEMBL)
TRIM24-p-2Y-FGFR1 fusion	Protein	O15164 (Uniprot-TrEMBL)
Tyrosine kinase inhibitors of overexpressed FGFR1	Complex	R-HSA-R-ALL-2023441 (Reactome)
Tyrosine kinase inhibitors of FGFR1 fusion mutants	Complex	R-HSA-R-ALL-2045079 (Reactome)
UBA52(1-76)	Protein	P62987 (Uniprot-TrEMBL)
UBB(1-76)	Protein	P0CG47 (Uniprot-TrEMBL)
UBB(153-228)	Protein	P0CG47 (Uniprot-TrEMBL)
UBB(77-152)	Protein	P0CG47 (Uniprot-TrEMBL)
UBC(1-76)	Protein	P0CG48 (Uniprot-TrEMBL)
UBC(153-228)	Protein	P0CG48 (Uniprot-TrEMBL)
UBC(229-304)	Protein	P0CG48 (Uniprot-TrEMBL)
UBC(305-380)	Protein	P0CG48 (Uniprot-TrEMBL)
UBC(381-456)	Protein	P0CG48 (Uniprot-TrEMBL)
UBC(457-532)	Protein	P0CG48 (Uniprot-TrEMBL)
UBC(533-608)	Protein	P0CG48 (Uniprot-TrEMBL)
UBC(609-684)	Protein	P0CG48 (Uniprot-TrEMBL)
UBC(77-152)	Protein	P0CG48 (Uniprot-TrEMBL)
Ub-(Y55/Y227)p-SPRY2	Complex	R-HSA-1370875 (Reactome)
Ub-Activated FGFR1 complex:Ub-p-FRS2	Complex	R-HSA-5654357 (Reactome)
Ub:Y55/Y227-pSPRY2:CBL	Complex	R-HSA-934572 (Reactome)
Ub	Complex	R-HSA-113595 (Reactome)
Y55/Y227-pSPRY2:CBL	Complex	R-HSA-934576 (Reactome)
ZMYM2-FGFR1 fusion	Protein	Q9UBW7 (Uniprot-TrEMBL)
ZMYM2-p-2Y-FGFR1 fusion	Protein	Q9UBW7 (Uniprot-TrEMBL)
activated FGFR1:PLCG1	Complex	R-HSA-5654155 (Reactome)
activated FGFR1:p-4Y-PLCG1	Complex	R-HSA-5654154 (Reactome)
p-4Y-PLCG1	Protein	P19174 (Uniprot-TrEMBL)
p-4Y-PLCG1	Protein	P19174 (Uniprot-TrEMBL)
p-5Y-FRS3	Protein	O43559 (Uniprot-TrEMBL)	The phospho-tyrosine positions for FRS2-beta were inferred by similarity to the analogous positions in FRS2-alpha. Five out of six tyrosine positions in alpha are present in beta.
p-6Y-FRS2	Protein	Q8WU20 (Uniprot-TrEMBL)
p-8T-FRS2	Protein	Q8WU20 (Uniprot-TrEMBL)
p-8Y- FGFR1 R576W	Protein	P11362 (Uniprot-TrEMBL)
p-8Y-FGFR1 K656E	Protein	P11362 (Uniprot-TrEMBL)
p-8Y-FGFR1 N546K	Protein	P11362 (Uniprot-TrEMBL)
p-8Y-FGFR1 P252S	Protein	P11362 (Uniprot-TrEMBL)	thought to increase # hydrogen bonds, increase ligand affinity and ligand binding range (Ruhe 2007)
p-8Y-FGFR1 P252T	Protein	P11362 (Uniprot-TrEMBL)	thought to increase # hydrogen bonds, increase ligand affinity and ligand binding range (Ruhe 2007)
p-8Y-FGFR1b	Protein	P11362-19 (Uniprot-TrEMBL)	While the existence of a "b" isoform of fibroblast growth factor receptor 1 is well established and its biochemical and functional properties have been extensively characterized (e.g., Mohammadi et al. 2005; Zhang et al. 2006), its amino acid sequence is not represented in reference protein sequence databases, except as the 47-residue polypeptide (deposited in GenBank as accession AAB19502) first used by Johnson et al. (1991) to distinguish the "b" and "c" isoforms of the receptor.
p-8Y-FGFR1c	Protein	P11362-1 (Uniprot-TrEMBL)
p-8Y-FGFR1c P252R	Protein	P11362-1 (Uniprot-TrEMBL)
p-FGFR1 fusion mutant dimers:PIK3R1	Complex	R-HSA-1839052 (Reactome)
p-FGFR1 fusion mutant dimers	Complex	R-HSA-1839020 (Reactome)
p-FGFR1 fusion mutant dimers	Complex	R-HSA-1839023 (Reactome)
p-FGFR1 mutant fusions:PI3K	Complex	R-HSA-1839055 (Reactome)
p-MEK:ERK	Complex	R-HSA-1268217 (Reactome)
p-MEK:p-ERK	Complex	R-HSA-1268207 (Reactome)
p-S,T-MAP2K2	Protein	P36507 (Uniprot-TrEMBL)
p-S111,S120-SPRY2	Protein	O43597 (Uniprot-TrEMBL)
p-S111,S120-SPRY2	Protein	O43597 (Uniprot-TrEMBL)
p-S112,S115-SPRY2	Protein	O43597 (Uniprot-TrEMBL)
p-S112,S121-SPRY2	Protein	O43597 (Uniprot-TrEMBL)
p-S218,S222-MAP2K1	Protein	Q02750 (Uniprot-TrEMBL)
p-S222,S226-MAP2K2	Protein	P36507 (Uniprot-TrEMBL)
p-STAT5	Complex	R-HSA-507929 (Reactome)
p-T,Y MAPK dimers	Complex	R-HSA-1268261 (Reactome)
p-T,Y MAPKs	Complex	R-HSA-169289 (Reactome)
p-T185,Y187-MAPK1	Protein	P28482 (Uniprot-TrEMBL)
p-T202,Y204-MAPK3	Protein	P27361 (Uniprot-TrEMBL)
p-T250,T255,T385,S437-MKNK1	Protein	Q9BUB5 (Uniprot-TrEMBL)
p-Y-GAB2	Protein	Q9UQC2 (Uniprot-TrEMBL)
p-Y177-BCR-pY-FGFR1 mutant:GRB2:p-GAB2:PIK3R1	Complex	R-HSA-1839048 (Reactome)
p-Y194,Y195,Y272-SHC1-1(156-583)	Protein	P29353-3 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2	Protein	P29353-2 (Uniprot-TrEMBL)
p-Y371-CBL	Protein	P22681 (Uniprot-TrEMBL)
p-Y371-CBL:GRB2	Complex	R-HSA-182964 (Reactome)
p-Y546,Y584-PTPN11	Protein	Q06124 (Uniprot-TrEMBL)
p-Y55,Y227-SPRY2	Protein	O43597 (Uniprot-TrEMBL)
p-Y694-STAT5A	Protein	P42229 (Uniprot-TrEMBL)
p-Y699-STAT5B	Protein	P51692 (Uniprot-TrEMBL)
p-Y701-STAT1	Protein	P42224 (Uniprot-TrEMBL)
p-Y705-STAT3	Protein	P40763 (Uniprot-TrEMBL)
p21 RAS:GDP	Complex	R-HSA-109796 (Reactome)
p21 RAS:GTP	Complex	R-HSA-109783 (Reactome)
pY-STAT1,3	Complex	R-HSA-1888197 (Reactome)
pY177-BCR-p-FGFR1 fusion mutant dimer	Complex	R-HSA-1839043 (Reactome)
pY177-BCR-p-FGFR1 fusion	Protein	P11274 (Uniprot-TrEMBL)
pY177-BCR-pY-FGFR1 mutant:GRB2:p-GAB1:PI3K	Complex	R-HSA-1839051 (Reactome)
pY177-BCR-pY-FGFR1 mutant:GRB2:p-GAB2	Complex	R-HSA-1839047 (Reactome)
pY177-BCR1-p-FGFR1 mutant:GRB2:GAB2	Complex	R-HSA-1839045 (Reactome)

Annotated Interactions

View all...

Source	Target	Type	Database reference	Comment
	ADP	Arrow	R-HSA-1268210 (Reactome)
	ADP	Arrow	R-HSA-1295609 (Reactome)
	ADP	Arrow	R-HSA-1839065 (Reactome)
	ADP	Arrow	R-HSA-1839067 (Reactome)
	ADP	Arrow	R-HSA-1839091 (Reactome)
	ADP	Arrow	R-HSA-1839098 (Reactome)
	ADP	Arrow	R-HSA-1839107 (Reactome)
	ADP	Arrow	R-HSA-1839110 (Reactome)
	ADP	Arrow	R-HSA-1839112 (Reactome)
	ADP	Arrow	R-HSA-1888198 (Reactome)
	ADP	Arrow	R-HSA-190427 (Reactome)
	ADP	Arrow	R-HSA-190429 (Reactome)
	ADP	Arrow	R-HSA-191062 (Reactome)
	ADP	Arrow	R-HSA-1982066 (Reactome)
	ADP	Arrow	R-HSA-2023455 (Reactome)
	ADP	Arrow	R-HSA-2023460 (Reactome)
	ADP	Arrow	R-HSA-5654149 (Reactome)
	ADP	Arrow	R-HSA-5654545 (Reactome)
	ADP	Arrow	R-HSA-5654560 (Reactome)
	ADP	Arrow	R-HSA-5654575 (Reactome)
	ADP	Arrow	R-HSA-5654578 (Reactome)
	ADP	Arrow	R-HSA-5654582 (Reactome)
	ADP	Arrow	R-HSA-5654587 (Reactome)
	ADP	Arrow	R-HSA-5654690 (Reactome)
	ADP	Arrow	R-HSA-5654692 (Reactome)
	ADP	Arrow	R-HSA-5655278 (Reactome)
	ADP	Arrow	R-HSA-5655290 (Reactome)
	ADP	Arrow	R-HSA-934559 (Reactome)
ATP			R-HSA-1268210 (Reactome)
ATP			R-HSA-1295609 (Reactome)
ATP			R-HSA-1839065 (Reactome)
ATP			R-HSA-1839067 (Reactome)
ATP			R-HSA-1839091 (Reactome)
ATP			R-HSA-1839098 (Reactome)
ATP			R-HSA-1839107 (Reactome)
ATP			R-HSA-1839110 (Reactome)
ATP			R-HSA-1839112 (Reactome)
ATP			R-HSA-1888198 (Reactome)
ATP			R-HSA-190427 (Reactome)
ATP			R-HSA-190429 (Reactome)
ATP			R-HSA-191062 (Reactome)
ATP			R-HSA-1982066 (Reactome)
ATP			R-HSA-2023455 (Reactome)
ATP			R-HSA-2023460 (Reactome)
ATP			R-HSA-5654149 (Reactome)
ATP			R-HSA-5654545 (Reactome)
ATP			R-HSA-5654560 (Reactome)
ATP			R-HSA-5654575 (Reactome)
ATP			R-HSA-5654578 (Reactome)
ATP			R-HSA-5654582 (Reactome)
ATP			R-HSA-5654587 (Reactome)
ATP			R-HSA-5654690 (Reactome)
ATP			R-HSA-5654692 (Reactome)
ATP			R-HSA-5655278 (Reactome)
ATP			R-HSA-5655290 (Reactome)
ATP			R-HSA-934559 (Reactome)
	Activated FGFR1 mutants:p-FRS2:GRB2:GAB1:PI3K	Arrow	R-HSA-5655263 (Reactome)
Activated FGFR1 mutants:p-FRS2:GRB2:GAB1:PI3K		mim-catalysis	R-HSA-5655290 (Reactome)
	Activated FGFR1 mutants:p-FRS2:GRB2:GAB1:PIK3R1	Arrow	R-HSA-5655240 (Reactome)
Activated FGFR1 mutants:p-FRS2:GRB2:GAB1:PIK3R1			R-HSA-5655263 (Reactome)
	Activated FGFR1:p-8T-FRS2	Arrow	R-HSA-5654560 (Reactome)
	Activated FGFR1:p-FRS2:GRB2:GAB1:PI3K	Arrow	R-HSA-5654591 (Reactome)
Activated FGFR1:p-FRS2:GRB2:GAB1:PI3K		mim-catalysis	R-HSA-5654690 (Reactome)
	Activated FGFR1:p-FRS2:GRB2:GAB1:PIK3R1	Arrow	R-HSA-5654592 (Reactome)
Activated FGFR1:p-FRS2:GRB2:GAB1:PIK3R1			R-HSA-5654591 (Reactome)
	Activated FGFR1:p-FRS2:GRB2:SOS1	Arrow	R-HSA-5654586 (Reactome)
Activated FGFR1:p-FRS2:GRB2:SOS1		mim-catalysis	R-HSA-5654392 (Reactome)
	Activated FGFR1:p-FRS2:p-PTPN11:GRB2:GAB1:PI3K	Arrow	R-HSA-5654596 (Reactome)
Activated FGFR1:p-FRS2:p-PTPN11:GRB2:GAB1:PI3K		mim-catalysis	R-HSA-5654692 (Reactome)
	Activated FGFR1:p-FRS2:p-PTPN11:p-CBL:GRB2	Arrow	R-HSA-5654673 (Reactome)
Activated FGFR1:p-FRS2:p-PTPN11:p-CBL:GRB2			R-HSA-5654672 (Reactome)
Activated FGFR1:p-FRS2:p-PTPN11:p-CBL:GRB2		mim-catalysis	R-HSA-5654672 (Reactome)
Activated FGFR1:p-FRS2:p-PTPN11			R-HSA-5654594 (Reactome)
Activated FGFR1:p-FRS2:p-PTPN11			R-HSA-5654673 (Reactome)
	Activated FGFR1:p-FRS2	Arrow	R-HSA-5654575 (Reactome)
Activated FGFR1:p-FRS2			R-HSA-5654592 (Reactome)
	Activated FGFR1:p-FRS3	Arrow	R-HSA-5654578 (Reactome)
	Activated FGFR1:p-FRS:PTPN11	Arrow	R-HSA-5654584 (Reactome)
Activated FGFR1:p-FRS:PTPN11			R-HSA-5654587 (Reactome)
Activated FGFR1:p-FRS:PTPN11		mim-catalysis	R-HSA-5654587 (Reactome)
Activated FGFR1:p-FRS:p-PTPN11		Arrow	R-HSA-5654392 (Reactome)
	Activated FGFR1:p-FRS:p-PTPN11	Arrow	R-HSA-5654587 (Reactome)
Activated FGFR1:p-FRS			R-HSA-5654584 (Reactome)
Activated FGFR1:p-FRS			R-HSA-5654586 (Reactome)
	Activated FGFR1:p-SHC1:GRB2:SOS1	Arrow	R-HSA-5654597 (Reactome)
Activated FGFR1:p-SHC1:GRB2:SOS1		mim-catalysis	R-HSA-5654600 (Reactome)
	Activated FGFR1:p-SHC1	Arrow	R-HSA-5654582 (Reactome)
Activated FGFR1:p-SHC1			R-HSA-5654597 (Reactome)
	Activated FGFR:p-FRS2:p-PTPN11:GRB2:GAB1:PIK3R1	Arrow	R-HSA-5654594 (Reactome)
Activated FGFR:p-FRS2:p-PTPN11:GRB2:GAB1:PIK3R1			R-HSA-5654596 (Reactome)
	Activated overexpressed FGFR1b homodimer	Arrow	R-HSA-1982066 (Reactome)
	Activated overexpressed FGFR1c homodimer	Arrow	R-HSA-5654545 (Reactome)
	Activated FGFR1 P252X mutants	Arrow	R-HSA-2023455 (Reactome)
	Activated FGFR1 mutant dimers with enhanced kinase activity	Arrow	R-HSA-2023460 (Reactome)
	Activated FGFR1 mutants and fusion:p-PLCG1	Arrow	R-HSA-1839098 (Reactome)
Activated FGFR1 mutants and fusion:p-PLCG1			R-HSA-1839100 (Reactome)
	Activated FGFR1 mutants and fusions:PLCG1	Arrow	R-HSA-1839094 (Reactome)
Activated FGFR1 mutants and fusions:PLCG1			R-HSA-1839098 (Reactome)
Activated FGFR1 mutants and fusions:PLCG1		mim-catalysis	R-HSA-1839098 (Reactome)
	Activated FGFR1 mutants and fusions	Arrow	R-HSA-1839100 (Reactome)
Activated FGFR1 mutants and fusions			R-HSA-1839094 (Reactome)
	Activated FGFR1 mutants:FRS2	Arrow	R-HSA-5655269 (Reactome)
Activated FGFR1 mutants:FRS2			R-HSA-5655278 (Reactome)
Activated FGFR1 mutants:FRS2		mim-catalysis	R-HSA-5655278 (Reactome)
	Activated FGFR1 mutants:p-FRS2	Arrow	R-HSA-5655278 (Reactome)
Activated FGFR1 mutants:p-FRS2			R-HSA-5655240 (Reactome)
Activated FGFR1 mutants:p-FRS2			R-HSA-5655266 (Reactome)
Activated FGFR1 mutants			R-HSA-5655269 (Reactome)
	Activated FGFR1:FRS2	Arrow	R-HSA-5654569 (Reactome)
Activated FGFR1:FRS2			R-HSA-5654560 (Reactome)
Activated FGFR1:FRS2			R-HSA-5654575 (Reactome)
Activated FGFR1:FRS2		mim-catalysis	R-HSA-5654575 (Reactome)
	Activated FGFR1:FRS3	Arrow	R-HSA-5654571 (Reactome)
Activated FGFR1:FRS3			R-HSA-5654578 (Reactome)
Activated FGFR1:FRS3		mim-catalysis	R-HSA-5654578 (Reactome)
	Activated FGFR1:SHC1	Arrow	R-HSA-5654573 (Reactome)
Activated FGFR1:SHC1			R-HSA-5654582 (Reactome)
Activated FGFR1:SHC1		mim-catalysis	R-HSA-5654582 (Reactome)
	Activated FGFR1	Arrow	R-HSA-5654165 (Reactome)
Activated FGFR1			R-HSA-5654167 (Reactome)
Activated FGFR1			R-HSA-5654569 (Reactome)
Activated FGFR1			R-HSA-5654571 (Reactome)
Activated FGFR1			R-HSA-5654573 (Reactome)
	Activated FGFR1b homodimer	Arrow	R-HSA-190427 (Reactome)
	Activated FGFR1c bound to FGF23:Klotho	Arrow	R-HSA-191062 (Reactome)
	Activated FGFR1c homodimer	Arrow	R-HSA-190429 (Reactome)
BCR-p-FGFR1 fusion mutant dimer			R-HSA-1839067 (Reactome)
BCR-p-FGFR1 fusion mutant dimer		mim-catalysis	R-HSA-1839067 (Reactome)
	BRAF	Arrow	R-HSA-1295604 (Reactome)
	CBL	Arrow	R-HSA-1295621 (Reactome)
CBL			R-HSA-1295622 (Reactome)
	FGF23 bound to Klotho and FGFR1c	Arrow	R-HSA-190268 (Reactome)
FGF23 bound to Klotho and FGFR1c			R-HSA-191062 (Reactome)
FGF23 bound to Klotho and FGFR1c		mim-catalysis	R-HSA-191062 (Reactome)
	FGFR1 mutants:p-FRS2:GRB2:SOS1	Arrow	R-HSA-5655266 (Reactome)
FGFR1 mutants:p-FRS2:GRB2:SOS1		mim-catalysis	R-HSA-5655326 (Reactome)
	FGFR1 P252X mutant dimers bound to FGFs	Arrow	R-HSA-2023451 (Reactome)
FGFR1 P252X mutant dimers bound to FGFs			R-HSA-2023455 (Reactome)
FGFR1 P252X mutant dimers bound to FGFs		mim-catalysis	R-HSA-2023455 (Reactome)
FGFR1 P252X mutants			R-HSA-2023451 (Reactome)
	FGFR1 fusion mutant dimers:TKIs	Arrow	R-HSA-1839039 (Reactome)
	FGFR1 fusion mutant dimers	Arrow	R-HSA-1839031 (Reactome)
FGFR1 fusion mutant dimers			R-HSA-1839039 (Reactome)
FGFR1 fusion mutant dimers			R-HSA-1839065 (Reactome)
FGFR1 fusion mutant dimers		mim-catalysis	R-HSA-1839065 (Reactome)
FGFR1 fusion mutants			R-HSA-1839031 (Reactome)
	FGFR1 mutant dimers with enhanced kinase activity	Arrow	R-HSA-2023456 (Reactome)
FGFR1 mutant dimers with enhanced kinase activity			R-HSA-2023460 (Reactome)
FGFR1 mutant dimers with enhanced kinase activity		mim-catalysis	R-HSA-2023460 (Reactome)
FGFR1 mutants with enhanced kinase activity			R-HSA-2023456 (Reactome)
FGFR1OP-p-FGFR1 fusion mutant dimer		mim-catalysis	R-HSA-1888198 (Reactome)
	FGFR1b homodimer bound to FGF	Arrow	R-HSA-190245 (Reactome)
FGFR1b homodimer bound to FGF			R-HSA-190427 (Reactome)
FGFR1b homodimer bound to FGF		mim-catalysis	R-HSA-190427 (Reactome)
	FGFR1b homodimer	Arrow	R-HSA-1982065 (Reactome)
FGFR1b homodimer			R-HSA-1982066 (Reactome)
FGFR1b homodimer		mim-catalysis	R-HSA-1982066 (Reactome)
FGFR1b-binding FGFs			R-HSA-190245 (Reactome)
FGFR1b			R-HSA-190245 (Reactome)
FGFR1b			R-HSA-1982065 (Reactome)
	FGFR1c homodimer bound to FGF	Arrow	R-HSA-190256 (Reactome)
FGFR1c homodimer bound to FGF			R-HSA-190429 (Reactome)
FGFR1c homodimer bound to FGF		mim-catalysis	R-HSA-190429 (Reactome)
	FGFR1c homodimer	Arrow	R-HSA-5654544 (Reactome)
FGFR1c homodimer			R-HSA-5654545 (Reactome)
FGFR1c homodimer		mim-catalysis	R-HSA-5654545 (Reactome)
FGFR1c-binding FGFs			R-HSA-190256 (Reactome)
FGFR1c-binding FGFs			R-HSA-2023451 (Reactome)
FGFR1c:KAL1		TBar	R-HSA-190256 (Reactome)
FGFR1c			R-HSA-190256 (Reactome)
FGFR1c			R-HSA-190268 (Reactome)
FGFR1c			R-HSA-5654544 (Reactome)
FRS2			R-HSA-5654569 (Reactome)
FRS2			R-HSA-5655269 (Reactome)
FRS3			R-HSA-5654571 (Reactome)
	GDP	Arrow	R-HSA-5654392 (Reactome)
	GDP	Arrow	R-HSA-5654600 (Reactome)
	GDP	Arrow	R-HSA-5655326 (Reactome)
GRB2-1:SOS1			R-HSA-5654586 (Reactome)
GRB2-1:SOS1			R-HSA-5654597 (Reactome)
GRB2-1:SOS1			R-HSA-5655266 (Reactome)
	GRB2-1	Arrow	R-HSA-1549564 (Reactome)
GRB2-1			R-HSA-1295613 (Reactome)
	GRB2:GAB1:PIK3R1	Arrow	R-HSA-177931 (Reactome)
GRB2:GAB1:PIK3R1			R-HSA-5654592 (Reactome)
GRB2:GAB1:PIK3R1			R-HSA-5654594 (Reactome)
GRB2:GAB1:PIK3R1			R-HSA-5655240 (Reactome)
GRB2:GAB1			R-HSA-177931 (Reactome)
GRB2:GAB2			R-HSA-1839095 (Reactome)
GTP			R-HSA-5654392 (Reactome)
GTP			R-HSA-5654600 (Reactome)
GTP			R-HSA-5655326 (Reactome)
HS		Arrow	R-HSA-190245 (Reactome)
HS		Arrow	R-HSA-190256 (Reactome)
HS		Arrow	R-HSA-190268 (Reactome)
HS			R-HSA-190245 (Reactome)
HS			R-HSA-190256 (Reactome)
HS			R-HSA-190268 (Reactome)
HS			R-HSA-2023451 (Reactome)
IL17RD-1		TBar	R-HSA-1268206 (Reactome)
IL17RD		TBar	R-HSA-1268210 (Reactome)
KAL1:HS		Arrow	R-HSA-190256 (Reactome)
Klotho bound to FGF23			R-HSA-190268 (Reactome)
	Overexpressed FGFR1:TKIs	Arrow	R-HSA-2023462 (Reactome)
Overexpressed FGFR1 homodimers			R-HSA-2023462 (Reactome)
	PI(3,4,5)P3	Arrow	R-HSA-1839091 (Reactome)
	PI(3,4,5)P3	Arrow	R-HSA-1839107 (Reactome)
	PI(3,4,5)P3	Arrow	R-HSA-5654690 (Reactome)
	PI(3,4,5)P3	Arrow	R-HSA-5654692 (Reactome)
	PI(3,4,5)P3	Arrow	R-HSA-5655290 (Reactome)
PI(3,4,5)P3			R-HSA-1839094 (Reactome)
PI(3,4,5)P3			R-HSA-5654167 (Reactome)
PI(4,5)P2			R-HSA-1839091 (Reactome)
PI(4,5)P2			R-HSA-1839107 (Reactome)
PI(4,5)P2			R-HSA-5654690 (Reactome)
PI(4,5)P2			R-HSA-5654692 (Reactome)
PI(4,5)P2			R-HSA-5655290 (Reactome)
PIK3CA			R-HSA-1839080 (Reactome)
PIK3CA			R-HSA-1839102 (Reactome)
PIK3CA			R-HSA-5654591 (Reactome)
PIK3CA			R-HSA-5654596 (Reactome)
PIK3CA			R-HSA-5655263 (Reactome)
PIK3R1			R-HSA-177931 (Reactome)
PIK3R1			R-HSA-1839078 (Reactome)
PIK3R1			R-HSA-1839114 (Reactome)
PLCG1			R-HSA-1839094 (Reactome)
PLCG1			R-HSA-5654167 (Reactome)
	PP2A (A:C)	Arrow	R-HSA-1295622 (Reactome)
	PP2A(A:C):S112/S121-pSPRY2	Arrow	R-HSA-934559 (Reactome)
PP2A(A:C):S112/S121-pSPRY2		TBar	R-HSA-1295609 (Reactome)
	PP2A(A:C):SPRY2	Arrow	R-HSA-1295599 (Reactome)
PP2A(A:C):SPRY2			R-HSA-1295609 (Reactome)
PP2A(A:C):SPRY2			R-HSA-934559 (Reactome)
	PP2A(A:C):Y55/Y227-pSPRY2	Arrow	R-HSA-1295609 (Reactome)
	PP2A(A:C):Y55/Y227-pSPRY2	Arrow	R-HSA-1549564 (Reactome)
PP2A(A:C):Y55/Y227-pSPRY2			R-HSA-1295613 (Reactome)
PP2A(A:C):Y55/Y227-pSPRY2			R-HSA-1295622 (Reactome)
PPA2A (A:C):S112/S115 p-SPRY2			R-HSA-1295632 (Reactome)
PPA2A (A:C):S112/S115 p-SPRY2		mim-catalysis	R-HSA-1295632 (Reactome)
	PPA2A (A:C):Y55/Y227 p-SPRY2:GRB2	Arrow	R-HSA-1295613 (Reactome)
PPA2A (A:C):Y55/Y227 p-SPRY2:GRB2			R-HSA-1549564 (Reactome)
	PPA2A(A:C):SPRY2	Arrow	R-HSA-1295632 (Reactome)
PPA2A(A:C):SPRY2			R-HSA-1295599 (Reactome)
PTPN11			R-HSA-5654584 (Reactome)
PTPN11		mim-catalysis	R-HSA-1549564 (Reactome)
	Phospho-MEK	Arrow	R-HSA-1268206 (Reactome)
	Pi	Arrow	R-HSA-1295632 (Reactome)
			R-HSA-1268206 (Reactome)	p-ERK1/2 dissociates from p-MEK1/2, allowing dimerization of the activated MAPKs and translocation to the nucleus. In FGFR signaling, there is evidence that this dissociation event is negatively regulated by the golgi membrane form of IL17RD, preventing the nuclear localization of activated ERK1/2.
			R-HSA-1268210 (Reactome)	MEK1/2 phosphorylate critical tyrosine and threonine residues on ERK1/2, activating the kinase activity of the MAPKs. In FGFR signaling, this reaction appears to be negatively regulated by IL17RD through an unknown mechanism, limiting the extent of MAPK signaling after FGF stimulation.
			R-HSA-1295599 (Reactome)	SPRY2 translocates to the plasma membrane upon activation of cells with FGF, and translocation is required for the inhibition of growth factor-stimulated cell migration, proliferation and differentiation. Translocation may be mediated by interactions with PIP2 in the membrane, palmitoylation of the C-terminal region of SPRY2 and/or interactions with caveolin-1.
			R-HSA-1295604 (Reactome)	MAPK-dependent serine phosphorylation of SPRY2 disrupts complex formation with B-RAF.
			R-HSA-1295609 (Reactome)	Sprouty 2 protein is phosphorylated on tyrosine residue 55. The ability of SRC kinase to catalyze this reaction has been demonstrated with purified proteins in vitro (Li et al. 2004) and in cultured cells with studies of the effects of SRC-family pharmacological inhibitors and of dominant-negative mutant SRC proteins (Mason et al. 2004). SRC kinase also phosphorylates numerous tyrosine residues in the C terminal region of SPRY2 including Y227, in response to FGF but not EGF stimulation.
			R-HSA-1295613 (Reactome)	Some evidence suggests that SPRY2 may exert its negative effect by binding to GRB2 and competing with the GRB2:SOS1 interaction that is required for MAPK activation. SPRY2 phosphorylation at Y55 is stimulated in response to both FGF and EGF, and is required for SPRY2 to act as a negative regulator of FGF signaling. Y55 is not thought to be a GRB2 binding site, however. Instead, phosphorylation at Y55 is thought to cause a conformational change in SPRY2 that reveals a cryptic PXXPXPR GRB2-docking site in the C-terminal of SPRY2. SPRY2 has also been shown to be phosphorylated at multiple tyrosine residues in its C-terminal in response to FGF, but not EGF, stimulation. This phosphorylation, in particular at residue 227, is thought to augment the ability of SPRY2 to inhibit FGF signaling through the MAPK cascade, although the mechanism remains to be elucidated.
			R-HSA-1295621 (Reactome)	After ubiquitination, CBL dissociates from SPRY2
			R-HSA-1295622 (Reactome)	The N terminal TKB domain of CBL binds to the phospho-tyrosine 55 of SPRY2, targeting SPRY2 for degradation by the 26S proteasome. Y55 is also a binding site for PP2A, which dephosphorylates numerous serine and threonine residues on SPRY2, allowing a conformational change that may promote a SPRY2:GRB2 interaction and limit the extent of MAPK activation following FGF stimulation.
			R-HSA-1295628 (Reactome)	After being phosphorylated, p-ERK1/2 dissociate from MEK1/2 and dimerize.
			R-HSA-1295632 (Reactome)	In unstimulated cells, SPRY2 has been shown to be phosphorylated on multiple serine and threonine residues. In these cells, SPRY2 exists in a complex with the regulatory and catalytic subunits (A and C, respectively) of the serine/threonine phosphatase PP2A. After stimulation with FGF, the catalytic activity of PP2A increases and the phosphatase dephophorylates SPRY at serine 112 and serine 115. This is thought to promote changes in tertiary structure that promote GRB2 binding and phosphorylation of Y55 and Y227.
			R-HSA-1295634 (Reactome)	Some evidence suggests that SPRY2 can exert its negative role on FGF signaling at the level of RAF activation. Hypophosphorylated SPRY2 binds to inactive B-RAF, preventing it from activating ERK signaling. MAPK activation results in phosphorylation of SPRY2 on six serine residues (S7, S42, S111, S120, S140 and S167), and inhibits B-RAF binding. Phosphorylation at S111 and S120 directly affects B-RAF binding while the remaining four sites appear to contribute indirectly. Oncogenic forms of B-RAF such as B-RAF V600E, which adopt active kinase conformations, do not associate with SPRY2, regardless of its phosphorylation status. This suggests that two mechanisms affect the SPRY2:B-RAF interaction: SPRY2 phosphorylation and B-RAF conformation.
			R-HSA-1549564 (Reactome)	PPTN11 (also known as SHP2) may exert its positive effects on MAPK activation in response to FGF stimulation by catalyzing the dephosphorylation of tyrosine resides on SPRY2. This dephosphorylation promotes dissociation of the GRB2/SPRY2 complex and as a consequence stimulates GRB2 association with the activated receptor, leading to sustained MAPK signaling.
			R-HSA-177931 (Reactome)	The Src homology 2 (SH2) domain of the phosphatidylinositol 3-kinase (PIK3) regulatory subunit (PIK3R1, i.e. PI3Kp85) binds to GAB1 in a phosphorylation-independent manner. GAB1 serves as a docking protein which recruits a number of downstream signalling proteins. PIK3R1 can bind to either GAB1 or phosphorylated GAB1.
			R-HSA-1839031 (Reactome)	8p11 myeloproliferative syndrome (EMS) is a myeloproliferative disorder that rapidly progresses to acute myeloid leukemia if not treated (reviewed in Jackson, 2010, Knights and Cook, 2010). A characteristic feature of EMS is the presence of fusion proteins that contain the kinase domain of FGFR1 and the oligomerization domain of an unrelated protein. This is believed to promote the ligand independent dimerization and activation of the kinase domain. To date, there are 11 identified partners that form fusion proteins with FGFR1 in EMS: ZMYM2 (Xiao, 1998; Popovici, 1998; Reiter, 1998; Ollendorff, 1999; Xiao, 2000), FGFR1OP1 (Popovici, 1999), CNTRL (Guasch, 2000), BCR (Demiroglu, 2001), FGFR1OP2 (Grand, 2004), TRIM24 (Belloni, 2005), CUX1 (Wasag, 2011), MYO18A (Walz, 2005), CPSF6 (Hidalgo-Curtis, 2008), HERV-K (Guasch, 2003) and LRRFIP1 (Soler, 2009).
			R-HSA-1839039 (Reactome)	In a murine mouse model of ZNF198-FGFR1-induced EMS, treatment with the FGFR-inhibitor Midostaurin (PKC412) resulted in prolonged survival (Chen, 2004). Similarly, growth of ZNF-198-FGFR1-, FGFR1OP2-FGFR1-, and BCR-FGFR1-expressing lines is blocked by treatment with FGFR-inhibitors (Demiroglu, 2001; Gu, 2006; Chase, 2007; Zhen, 2007; Wasag, 2011).
			R-HSA-1839065 (Reactome)	After ligand-independent dimerization, FGFR1 fusions are trans-autophosphorylated on tyrosine residues (see for instance Popovici, 1998; Ollendorff, 1999; Guasch, 2000). Although the sites of tyrosine phosphorylation have not been mapped in the context of the fusion proteins, at least some of the same residues appear to be phosphorylated as in full length FGFR1. For instance, phospho-specific antibodies have demonstrated that TRIM24 is phosphorylated on Y653 and Y654, the activation loop tyrosines of FGFR1 (Belloni, 2005). Likewise, FGFR1 fusions with ZMYM2, BCR, FGFR1OP and TRIM24 all result in recruitment and phosphorylation of PLCgamma, and where mutational studies have been performed, mutation of the PLCgamma binding site Y766 has been shown to abrogate this signaling (Roumiantsev, 2004, Lelievre, 2008, Chase, 2007). In the case of BCR-FGFR1, the BCR moiety of the fusion protein has also been shown to be phosphorylated on at least one tyrosine residue, Y177, which results in the recruitment of GRB2 (Roumiantsev, 2004).
			R-HSA-1839067 (Reactome)	Unique among FGFR1 fusion proteins, which generally give rise to an atypical myeloproliferative syndrome (EMS) (reviewed in Jackson, 2010), the BCR-FGFR1 fusion results in a more typical chronic myeloid leukemia (CML). Although both EMS and CML activate PLCgamma signaling, and mutation of the FGFR1 Y766 PLCgamma binding site attenuates both diseases, CML-specific signaling also appears to be mediated through the BCR portion of the fusion protein. BCR Y177 binds GRB2-GAB1 and induces CML-like leukemia in mice, while expression of a Y177F BCR-FGFR1 fusion induces EMS-like disease (Roumiantsev, 2004).
			R-HSA-1839078 (Reactome)	Activation of the PI3K signaling pathway has been demonstrated for a number of FGFR1 fusion proteins and inhibitors of this pathway impair the proliferative and survival function of the fusions (Guasch, 2001; Demiroglu, 2001; Chen, 2004; Lelievre, 2008). FGFR1 fusions lack the FRS2-binding site of the full length protein, so the mechanism of PI3K recruitment is unclear. Unlike BCR-FGFR1, which has been shown to recruit GRB2 through the BCR Y177 site, GRB2 did not co-precipitate with the ZMYM2-FGFR1 fusion (Roumianetsev, 2004). In the case of FOP-FGFR1, Y730 has been shown to be required for the recruitment of the p85 subunit of PI3K; however, CEP110-FGFR1, which contains Y730 in the context of the same pYXXM motif, was not shown to recruit p85 at the centrosome (Guasch, 2001).
			R-HSA-1839080 (Reactome)	Activation of the PI3K pathway has been demonstrated in the case of ZMYM2-FGFR1 (Chen, 2004), BCR-FGFR1 (Demiroglu, 2001) and FOP-FGFR1 (Guasch, 2001), and is presumed to occur to a greater or lesser extent in other FGFR1 fusions as well (reviewed in Jackson, 2010). Activation of the PI3K pathway suggests that the PIK3CA catalytic subunit must be recruited to the fusion protein.
			R-HSA-1839091 (Reactome)	Once recruited to the activated receptor, PI3K phosphorylates PIP2 to PIP3, leading to activation of AKT signaling. PI3K signaling has been demonstrated in ZMYM2-, FOP- and BCR-FGFR1 fusions (Chen, 2004; Demiroglu, 2001; Guasch, 2001), as well as downstream of a number of other FGFR mutants (see for instance, Byron, 2008; Kunii, 2008; Agazie, 2003; Takeda, 2007).
			R-HSA-1839094 (Reactome)	Although it has not been rigourously established, there is some evidence that PLC-gamma signaling may be activated after autophosphorylation of some FGFR mutants, analagous to the wild type receptor (see for instance, Hart, 2000; Chen, 2005; Cha, 2008; di Martino, 2009; Gartside, 2009; Cross, 2000; Hatch, 2006). The extent to which each of the mutants activates this pathway and to which proliferation and tumorigenesis relies on PLC-gamma dependent signaling, remains to be more firmly established. FGFR1 fusions with ZMYM2, BCR, FGFR1OP and TRIM24 all result in recruitment and phosphorylation of PLCgamma, and where mutational studies have been performed, mutation of the PLCgamma binding site Y766 has been shown to abrogate this signaling (Guasch, 2001; Roumiantsev, 2004, Lelievre, 2008, Chase, 2007). In the case of BCR-FGFR1 and ZMYM2-FGFR1, mutation of the PLCgamma binding site significantly decreased the transformative phenotype of the FGFR1 fusion (Roumiantsev, 2004).
			R-HSA-1839095 (Reactome)	Proliferation of BCR-FGFR1 fusion proteins is blocked by treatment with the PI3K inhibitor LY294002, suggesting the activation of this pathway downstream of BCR-FGFR1 phosphorylation. Y177 has been shown to be a binding site for GRB2 and to be required for the both the phosphorylation of GAB2 and the development of CML-like disease (Roumiantsev, 2004, Demiroglu, 2001). By analogy with studies in BCR-ABL, where mutation of Y177 abrogates recruitment of PI3K activity to the fusion protein (Sattler, 2002), this suggests that Y177 may serve as a docking site for a complex of GRB2:GAB1:PI3K in the context of BCR-FGFR1 as well.
			R-HSA-1839098 (Reactome)	By analogy with the wild-type pathway, PLC-gamma is presumed to be phosphorylated by activated FGFR mutants, resulting in PLC-gamma activation, stimulation of phosphatidyl inositol hydrolysis and generation of two second messengers, diacylglycerol and inositol (1,4,5) P3.
			R-HSA-1839100 (Reactome)	Dissociation from the activated receptor quickly follows phosphorylation of PLC-gamma. Phosphorylated PLC-gamma catalyzes the hydrolysis of phosphatidylinositol(4, 5)bisphosphate to generate two second messengers, diacylglycerol and inositol (1,4,5) triphosphate.
			R-HSA-1839102 (Reactome)	Activation of the PI3K pathway has been demonstrated in the case of ZMYM2-FGFR1 (Chen, 2004), BCR-FGFR1 (Demiroglu, 2001) and FOP-FGFR1 (Guasch, 2001), and is presumed to occur to a greater or lesser extent in other FGFR1 fusions as well (reviewed in Jackson, 2010). Activation of the PI3K pathway suggests that the PIK3CA catalytic subunit must be recruited to the fusion protein.
			R-HSA-1839107 (Reactome)	Once recruited to the activated BCR-FGFR1 fusion PI3K phosphorylates PIP2 to PIP3, leading to activation of AKT signaling (Roumiantsev, 2004; Demiroglu, 2001).
			R-HSA-1839110 (Reactome)	Recruitment of GAB2 to the BCR-FGFR1 fusion protein results in GAB2 phosphorylation (Roumiatnetsev, 2004). As in the case of BCR-ABL (Sattler, 2002), recruitment and phosphorylation of GAB2 is dependent on BCR residue Y177. Deletion of Y177 abolishes GRB2 recruitment and converts the more aggressive MPD disorder induced by BCR-FGFR1 to the EMS characteristic of other FGFR1 fusions (Demiroglu, 2001; Roumianetsev, 2004)
			R-HSA-1839112 (Reactome)	Activation of a subset of FGFR1-fusions (ZMYM2, BCR, FGFR1OP2 and CUX) has been shown to result in downstream phosphorylation of STAT5 proteins at Y694. This phosphorylation is dependent on the FGFR1 fusion, as the STAT5 phosphorylation is abrogated in the presence of an FGFR1-kinase dead fusion (Heath and Cross, 2004; Smedley, 1999; Chase, 2007; Wasage, 2011).
			R-HSA-1839114 (Reactome)	Based on analogy with studies of the BCR-ABL fusion, phosphorylated GAB2 recruits the regulatory subunit of PI3K to the BCR-FGFR1 fusion (Sattler, 2002; Demiroglu, 2001; Roumiantsev, 2004).
			R-HSA-1888198 (Reactome)	Expression of FGFR1OP-FGFR1 in both Ba/F3 and Cos-1 cells leads to phosphorylation of STAT1 and STAT3 but not STAT5, and to activation of a STAT1/3-responsive reporter when expressed in NIH3T3 cells (Guasch, 2001). Activation of STAT proteins has also been shown to be oncogenic in the context of derivatives of FGFR1, 3 and 4 that lack the extracellular domain and are are targetted to the plasma membrane by a myristylation signal (Hart et al, 2000).
			R-HSA-190245 (Reactome)	In this reaction, FGF receptor in the plasma membrane binds an associating extracellular ligand, a requisite step for subsequent activation. The resulting complex consists of dimerized receptor, two ligand molecules, and heparan sulfate. NCAM and other members of the CAM protein family directly or indirectly modulate this interaction in a variety of neural tissues. The details of this interaction in vivo have not been definitively established at the molecular level, but are thought to play a central role in the regulation of the development of these tissues.
			R-HSA-190256 (Reactome)	In this reaction, FGF receptor in the plasma membrane binds an associating extracellular ligand, a requisite step for subsequent activation. The resulting complex consists of dimerized receptor, two ligand molecules, and heparan sulfate.
			R-HSA-190268 (Reactome)	In this reaction, FGF receptor in the plasma membrane binds an associating extracellular ligand, a requisite step for subsequent activation. The resulting complex consists of dimerized receptor, two ligand molecules, and heparan sulfate.
			R-HSA-190427 (Reactome)	Studies have mapped 8 tyrosine residues in the cytoplasmic domain of FGFR1 that are important for signaling. Autophosphorylation of residues 653 and 654, located in the activation loop of the kinase, is necessary to maintain the receptor in the active state. Phosphorylation of other tyrosine residues by the intrinsic protein tyrosine kinase activity of the activated receptor creates binding sites on its cytoplasmic tail for membrane bound docking proteins to gather intracellular signaling mediators.
			R-HSA-190429 (Reactome)	Studies have mapped 8 tyrosine residues in the cytoplasmic domain of FGFR1 that are important for signaling. Autophosphorylation of residues 653 and 654, located in the activation loop of the kinase, is necessary to maintain the receptor in the active state. Phosphorylation of other tyrosine residues by the intrinsic protein tyrosine kinase activity of the activated receptor creates binding sites on its cytoplasmic tail for membrane bound docking proteins to gather intracellular signaling mediators.
			R-HSA-191062 (Reactome)	Studies have mapped 8 tyrosine residues in the cytoplasmic domain of FGFR1 that are important for signaling. Autophosphorylation of residues 653 and 654, located in the activation loop of the kinase, is necessary to maintain the receptor in the active state. Phosphorylation of other tyrosine residues by the intrinsic protein tyrosine kinase activity of the activated receptor creates binding sites on its cytoplasmic tail for membrane bound docking proteins to gather intracellular signaling mediators.
			R-HSA-1982065 (Reactome)	FGFR1-amplified lung cancer and breast cancer cells show strong phosphorylation of FGFR1 and do not show elevated levels of FGF ligand, suggesting that these receptors can undergo ligand-independent activation. Phosphorylation is enhanced in the presence of exogenous ligand, supporting the notion that overexpressed FGFR1 can be activated by both ligand- and ligand-independent pathways (Koziczak, 2004; Dutt, 2008; Weiss, 2010). The biochemical consequences of overexpression of FGFR1 in other cancer types remain to be determined (reviewed in Turner and Gross, 2010; Wesche, 2011.
			R-HSA-1982066 (Reactome)	FGFR1-amplified lung cancer and breast cancer cells show strong phosphorylation of FGFR1 and do not show elevated levels of FGF ligand, suggesting that these receptors can undergo ligand-independent activation. Phosphorylation is enhanced in the presence of exogenous ligand, supporting the notion that overexpressed FGFR1 can be activated by both ligand- and ligand-independent pathways (Koziczak, 2004; Dutt, 2008; Weiss, 2010). The biochemical consequences of overexpression of FGFR1 in other cancer types remain to be determined (reviewed in Turner and Gross, 2010; Wesche, 2011.
			R-HSA-2023451 (Reactome)	The missense mutation C775G in exon 5 of FGFR1 encodes a Pro252R gain-of-function mutation that causes Pfeiffer syndrome, an autosomal dominant disorder characterized by premature fusion of bones in the skull and syndactyly of the hands and feet (Muenke, 1994). FGFR1 P252R binds to FGF1, FGF2, FGF4, and FGF6 with 2-5 fold-enhanced affinity, and with 30-fold affinity to FGF9. The enhanced ligand-affinity of the mutant receptor is the result of an additional set of ligand-receptor hydrogen bonds; in particular for FGF9, the additional receptor contacts are thought to compete with FGF9 autoinhibitory dimerization (Ibrahimi, 2004a). The increase in ligand-binding affinity in the absence of an expansion of ligand binding range is thought to account for the milder limb phenotype of Pfeiffer syndrome relative to FGFR2-mediated Apert syndrome (Yu, 2000; Ibrahimi, 2004b). Somatic mutations in FGFR1 at P252 have also been identified in melanoma (P252S; Ruhe, 2007) and in lung cancer (P252T; Davies, 2005). Based on analogy to the FGFR1 P252R mutation that is found in Pfeiffer syndrome, these mutations are also predicted to increase the ligand-binding affinity of the receptor and to result in increased signaling, although this remains to be directly demonstrated for the S/T alleles (Ibrahimi, 2004a).
			R-HSA-2023455 (Reactome)	FGFR1 gain-of-function mutations at P252 that result in increased binding affinity to ligand are presumed to be phosphorylated on the same sites as the wild-type receptor, although this has not been demonstrated (Ibrahimi, 2004a).
			R-HSA-2023456 (Reactome)	Large scale genomic characterization of glioblastoma tumors has identified three point mutants in the kinase domain of FGFR1: N546K, R576W and K656E (Rand, 2005, TCGA, 2008), representing the first kinase domain point mutants identified in this gene in any cancer. These mutants are believed or have been shown to have enhanced kinase activity and to be able to function in a ligand-independent manner (Petiot, 2002; Lew, 2009; Raffioni, 1998, Rand, 2005; Hart, 2000)
			R-HSA-2023460 (Reactome)	The three kinase domain mutants of FGFR1 that have been identified in glioblastoma are predicted or have been shown to result in enhanced kinase activity. The N546K (Rand, 2005) residue lies in a stretch of 9 amino acids that are conserved between all four FGFRs. Mutation of the paralogous residue in FGFR3 (N540K) has been shown to result in weak ligand-independent contstitutive activation in the autosomal disorder hypochodroplasia (Raffioni, 1998). In FGFR2 mutation of the paralogous residue to lysine has been identified in endometrial cancer and been shown to result in enhanced kinase activity (Dutt, 2008; Pollock, 2008); germline mutations at this site in FGFR2 are also associated with the development of Crouzon and Pfeiffer syndromes (Kan, 2002). The FGFR1 N546K mutations has accelerated rates of autophosphorylation and supports transformation when transfected into Rat-1 cells (Lew, 2009). The FGFR1 K656E (TCGA, 2008) mutation is paralogous to activating mutations in FGFR3 kinase domain associated with the development of thanatophoric dysplasias (Tavormina, 1999; Bellus, 2000; Hart, 2000), and has itself been shown to activating when expressed in neural crest cells (Petiot, 2002). The FGFR1 R576W (Rand, 2005) mutation increases the hydrophobicity of the receptor, and is postulated to enhance protein-protein interactions and thereby increase the likelihood of autophosphorylation of adjacent tyrosine residues, although this has not been explicitly demonstrated.
			R-HSA-2023462 (Reactome)	Treatment of FGFR1-amplified lung and breast cancer cell lines with the in vitro reagents PD173704, SU5402 and FIIN-1 inhibits proliferation, while cells expressing wild-type levels of FGFR1 are insensitive to inhibitors, suggesting that amplified FGFR1 may be a suitable therapeutic target in some cancer lines (Weiss, 2010; Reis-Filho, 2006; Dutt, 2011; Turner, 2010). In fact, a number of other small molecule inhibitors, including Dovitinib and AZD4547, are currently in clinical trials for treatment of FGFR1-amplified cancers (reviewed in Turner and Grose, 2010; Wesche, 2011; http://ClinicalTrials.gov)
			R-HSA-5654149 (Reactome)	PLC gamma is phosphorylated by activated FGFR, resulting in PLC gamma activation, stimulation of phosphatidyl inositol hydrolysis and generation of two second messengers, diacylglycerol and inositol (1,4,5) P3. Tyrosine phosphorylation of PLCgamma by FGFR4 is weaker than that seen by other isoforms of FGFR.
			R-HSA-5654165 (Reactome)	Dissociation from the activated receptor quickly follows phosphorylation of PLC-gamma. Phosphorylated PLC-gamma catalyzes the hydrolysis of phosphatidylinositol(4, 5)bisphosphate to generate two second messengers, diacylglycerol and inositol (1,4,5) triphosphate.
			R-HSA-5654167 (Reactome)	Recruitment of PLC-gamma by FGF receptors has been best studied in FGFR1c signaling, where it has been shown that autophosphorylation of Tyr766 in the C-terminal tail of FGFR1c creates a specific binding site for the SH2 domain of PLC-gamma. A mutant FGFR1c in which Y766 is replaced by phenylalanine is unable to activate PI hydrolysis and Ca2+ release in response to FGF stimulation. Membrane recruitment of PLC-gamma is also aided by binding of the Pleckstrin homology (PH) domain of this enzyme to PtIns(3,4,5) P3 molecules that are generated in response to PI-3 kinase stimulation. By sequence comparison, Y766 is conserved in all FGFR isoforms, and PLC-gamma signaling is observed, to a greater or lesser extent, downstream of all FGFR receptors upon stimulation with FGFs.
			R-HSA-5654392 (Reactome)	SOS, recruited by GRB2:p-FRS2 to activated FGFR, activates RAS nucleotide exchange from the inactive GDP-bound to the active GTP-bound state.
			R-HSA-5654544 (Reactome)	FGFR1-amplified lung cancer and breast cancer cells show strong phosphorylation of FGFR1 and do not show elevated levels of FGF ligand, suggesting that these receptors can undergo ligand-independent activation. Phosphorylation is enhanced in the presence of exogenous ligand, supporting the notion that overexpressed FGFR1 can be activated by both ligand- and ligand-independent pathways (Koziczak, 2004; Dutt, 2008; Weiss, 2010). The biochemical consequences of overexpression of FGFR1 in other cancer types remain to be determined (reviewed in Turner and Gross, 2010; Wesche, 2011.
			R-HSA-5654545 (Reactome)	FGFR1-amplified lung cancer and breast cancer cells show strong phosphorylation of FGFR1 and do not show elevated levels of FGF ligand, suggesting that these receptors can undergo ligand-independent activation. Phosphorylation is enhanced in the presence of exogenous ligand, supporting the notion that overexpressed FGFR1 can be activated by both ligand- and ligand-independent pathways (Koziczak, 2004; Dutt, 2008; Weiss, 2010). The biochemical consequences of overexpression of FGFR1 in other cancer types remain to be determined (reviewed in Turner and Gross, 2010; Wesche, 2011.
			R-HSA-5654560 (Reactome)	FRS2 has 8 canonical MAPK phosphorylation sites which are phosphorylated by activated ERK1/2 after FGF stimulation. Phosphorylation of these 8 threonine residues counteracts the activating effect of tyrosine phosphorylation of FRS2, although the exact mechanism for this negative regulation is not known. Expression of a version of FRS2 in which the 8 threonine residues are mutated to valine results in enhanced tyrosine phosphorylation of FRS2, enhanced GRB2-SOS1 recruitment and a more sustained MAPK response. The 8 threonine residues are not conserved in FRS3; as a result, signaling through FRS3 complexes do not appear to be subject to this downregulation.
			R-HSA-5654569 (Reactome)	FRS2 (also known as FRS2alpha) is broadly expressed in adult and fetal tissues. Membrane-bound FRS2 interacts with FGFR as a first step in the phosphorylation of this docking protein. The juxtamembrane binding site for FRS2 does not contain tyrosine, so binding may be independent of receptor activation and/or constitutive. Activation of the FGFR receptor is required for FRS2 phosphorylation and subsequent recruitment of downstream effectors.
			R-HSA-5654571 (Reactome)	FRS3 (also known as FRS2beta) is predominantly expressed in the developing and adult neuroepithelium. As is the case for FRS2 (also known as FRS2alpha), binding of FRS3 to FGFR may be constitutive and/or independent of receptor activation. Elements of the downstream signaling mediated by the two FRS family members appear to be at least partially conserved, as FRS3 is phosphorylated upon FGF stimulation, binds PPTN11/SHP2 and GRB2 and results in ERK activation. Moreover, expression of FRS3 in FRS2-/- MEFs restores ERK activation.
			R-HSA-5654573 (Reactome)	Although a role for SHC1 in FGF signalling has been implicated in many studies, it is not clear that SHC1 interacts directly with the receptor.
			R-HSA-5654575 (Reactome)	FRS2 (also known as FRS alpha is activated through tyrosine phosphorylation catalyzed by the protein kinase domain of the activated FGFR. FRS2 contains four binding sites for the adaptor protein GRB2 at residues Y196, Y306, Y349 and Y392, and two binding sites for the protein tyrosine phosphatase PPTN11/SHP2 at residues Y436 and Y471. Different FGFR isoforms may generate different phosphorylation patterns on FRS2 leading to alternate downstream signaling.
			R-HSA-5654578 (Reactome)	FRS3 (also known as FRS2 beta) is activated through tyrosine phosphorylation catalyzed by the protein kinase domain of the activated FGFR. By sequence comparison, FRS3 has the 2 PPTN11/SHP2-binding sites and has three of the four GRB2-binding sites.
			R-HSA-5654582 (Reactome)	The p46 and p53 isoforms of SHC1 have been shown to be phosphorylated upon FGF stimulation. Three consensus RTK phosphoryation sites are present in SHC1, although phosphorylation of these specific tyrosine residues has not been explicitly demonstrated in response to FGF stimulation. In contrast, the p66 isoform of SHC1 does not appear to undergo FGF-dependent phosphorylation.
			R-HSA-5654584 (Reactome)	p-FRS2 has two PPTN11/SHP2-binding sites at pY436 and pY471.
			R-HSA-5654586 (Reactome)	Tyrosine phosphorylated FRS2 recruits GRB2:SOS1 complex by means of the SH3 domain of GRB2, leading to RAS-MAP kinase activation. The FRS2:GRB2-mediated pathway plays a minor role in the activation of RAS-MAP kinase pathway compared to that mediated by FRS2:PPTN11.
			R-HSA-5654587 (Reactome)	Tyrosine phosphorylation of PPTN11/SHP2 by FGFR kinase is required for activation of the phosphatase activity of PPTN11 and for downstream signaling. Tyrosine phosphorylated PPTN11 plays a major role in the activation of RAS-MAP kinase pathway, although the precise role is not yet clear.
			R-HSA-5654591 (Reactome)	The 110 kDa catalytic subunit (PIK3CA) binds to the 85 kDa regulatory subunit (PIK3R1) to create the active PIK3.
			R-HSA-5654592 (Reactome)	The direct GRB2-binding sites of FRS2 have a major role in activation of the PI3K pathway.
			R-HSA-5654594 (Reactome)	p-PPTN11 recruits GRB2-GAB1 to the activated receptor.
			R-HSA-5654596 (Reactome)	The 110 kDa catalytic subunit (PIK3CA) binds to the 85 kDa regulatory subunit (PIK3R1) to create the active PIK3.
			R-HSA-5654597 (Reactome)	Phosphorylated SHC1 links FGFR to Grb2 (Klint et al. 1995) leading to the formation of a signaling complex including Shc, Grb2 and Sos. Transformation of NIH 3T3 cells with v-Src produced a strong constitutive association of FGFR1 with Shc, Grb2 and Sos (Curto et al. 1998) suggesting Src involvement. Recruitment of Grb2-Sos links FGFR to the Ras pathway.
			R-HSA-5654600 (Reactome)	SOS, recruited by GRB2:p-FRS2 to activated FGFR, activates RAS nucleotide exchange from the inactive GDP-bound to the active GTP-bound state.
			R-HSA-5654672 (Reactome)	Grb2 bound to tyrosine phosphorylated FRS2 forms a ternary complex with Cbl through the binding of the SH3 domains of Grb2 to a proline rich region in Cbl. Grb2-mediated recruitment of Cbl results in ubiquitination of FGFR and FRS2. Cbl is a multidomain protein that posses an intrinsic ubiquitin ligase activity and also functions as a platform for recruitment of a variety of signaling proteins. Multiple mechanisms appear to be required for downregulation of FGFR, as internalization of the receptor is reduced but not abolished if recruitment of CBL to FRS2 is compromised by mutation of GRB2-binding sites.
			R-HSA-5654673 (Reactome)	The ubiquitin ligase CBL exists in a complex with GRB2 and is recruited to tyrosine-phosphorylated FRS2 after FGF stimulation. In addition to promoting the ubiquitination, endocytosis, and degradation of the activated receptor complex, recruitment of the p-CBL:GRB2 complex seems to attenuate FGFR signaling by competing with GRB2:SOS1 for binding to the direct GRB2-binding sites on p-FRS2.
			R-HSA-5654690 (Reactome)	Once recruited to the membrane, PI3K catalyzes the phosphorylation of PI(4,5)P2 to PI(3,4,5)P3.
			R-HSA-5654692 (Reactome)	Once recruited to the activated receptor, PI3K phosphorylates PIP2 to PIP3, leading to activation of AKT signaling. PI3K signaling has been demonstrated in ZMYM2-, FOP- and BCR-FGFR1 fusions (Chen, 2004; Demiroglu, 2001; Guasch, 2001), as well as downstream of a number of other FGFR mutants (see for instance, Byron, 2008; Kunii, 2008; Agazie, 2003; Takeda, 2007).
			R-HSA-5655240 (Reactome)	FGFR1-amplified cells derived from lung cancer patients show phosphorylation of AKT and S6, demonstrating the activation of the PI3K signaling pathway in these lines. Inhibition of FGFR1 phosphorylation by treatment with the in vitro reagent PD173074 did not abrogate the phosphorylation of these substrates, however, indicating that the PI3K pathway is not the major signaling pathway activated by amplified FGFR1 (Weiss, 2010; Dutt, 2011). Activation of the PI3K pathway has also been demonstrated downstream of other FGFR mutants (see for instance, Agazie, 2003; Kunii, 2008, Takeda, 2007; Byron, 2008; Demiroglu, 2001; Guasch, 2001; Chen, 2004); however not all mutants activate the PI3K pathway to the same extent and in the case of the rhabdomyosarcoma FGFR4 mutants K535 and E550, phosphorylation of AKT is actually reduced compared to wild-type signaling (Taylor, 2009).
			R-HSA-5655263 (Reactome)	Activation of the PI3K pathway has been demonstrated downstream of a number of FGFR mutants (reviewed in Wesche, 2001; see for instance, Agazie, 2003; Kunii, 2008; Takeda, 2007; Chen, 2004; Demiroglu, 2001; Guasch, 2001; Byron, 2008), and is presumed to occur in a manner analogous to the wild-type receptor.
			R-HSA-5655266 (Reactome)	Activation of FGFR mutants has in some cases been shown to result in phosphorylation of both FRS2 (also known as FRS2alpha) and ERK1/2, suggesting activation of the MAPK pathway through wild-type like recruitment of the GRB2-SOS1 complex (reviewed in Wesche, 2011; see for instance, Weiss, 2010; Dutt, 2011; Raffioni, 1998; Hart, 2000).
			R-HSA-5655269 (Reactome)	After activation, FGFR mutants are presumed to recruit FRS2 (also known as FRS2alpha). This has been demonstrated in some cases (see for instance Ahmed, 2008; Weiss, 2010; Dutt, 2008; Dutt, 2011; Cha, 2009; Qing, 2009; Bai, 2010 ) and is inferred to occur in others by analogy with the wild-type receptor.
			R-HSA-5655278 (Reactome)	After recruitment to activated FGFR mutants, FRS2 is believed to be phosphorylated, potentially on all 6 of the tyrosines phosphorylated by wild-type FGFRs. Phosphorylation of FRS2 by FGFR has been demonstrated in some cases (see for instance Qing, 2009; Bai, 2010; Ahmed, 2008; Raffioni, 1998) and is inferred to occur in others based on activation of downstream signaling modules (reviewed in Wesche, 2011; Turner and Grose, 2010).
			R-HSA-5655290 (Reactome)	Once recruited to the activated receptor, PI3K phosphorylates PIP2 to PIP3, leading to activation of AKT signaling. PI3K signaling has been demonstrated in ZMYM2-, FOP- and BCR-FGFR1 fusions (Chen, 2004; Demiroglu, 2001; Guasch, 2001), as well as downstream of a number of other FGFR mutants (see for instance, Byron, 2008; Kunii, 2008; Agazie, 2003; Takeda, 2007).
			R-HSA-5655326 (Reactome)	Activation of Erk1/2 downstream of FGFR mutants suggests that, as is the case for WT FGFR, FGFR mutant-associated SOS1 activates RAS nucleotide exchange from the inactive GDP-bound to the active GTP-bound state (see for instance, Weiss, 2010; Dutt, 2011; Raffioni, 1998; Cha, 2009; Hart, 2000; Turner, 2010; Kunii, 2008; Byron, 2008; Roidl, 2010; Chesi, 2001; Ronchetti, 2001; reviewed in Wesche, 2011).
			R-HSA-934559 (Reactome)	In humans, the phosphorylated MNK1 kinase phosphorylates the adaptor protein Sprouty2 on Ser112 and Ser121, and also at some other serine and threonine residues. MNK1 appears not to form a complex with Sprouty2. Some of these (including the two main sites mentioned above) conform to the serine-containing consensus sites for phosphorylation by MNK1 kinase (K/R-X-X-S, R-X-S). It appears that serine phosphorylation is required to protect Sprouty2 from degradation. In the absence of serine phosphorylation, phosphorylation of Tyr55 and subsequent binding to E3 ubiquitin ligase, CBL, is enhanced. Serine phosphorylation of Sprouty2 appears to stabilise the protein by interfering with its potential phosphorylation of Tyr55 (Sprouty2 appears to be a poor substrate for c-Src kinase) in response to growth factor stimulation.
			R-HSA-934604 (Reactome)	In humans, the phosphorylated adaptor protein Sprouty2 is ubiquitinated by the E3 ubiquitin ligase CBL, marking it for degradation by the 26S proteasome.
	S111/S120 p-SPRY2:B-RAF	Arrow	R-HSA-1295634 (Reactome)
S111/S120 p-SPRY2:B-RAF			R-HSA-1295604 (Reactome)
SHC1 p46,p52			R-HSA-5654573 (Reactome)
SPRY2:B-RAF			R-HSA-1295634 (Reactome)
SRC-1		mim-catalysis	R-HSA-1295609 (Reactome)
STAT1,3			R-HSA-1888198 (Reactome)
STAT5			R-HSA-1839112 (Reactome)
Tyrosine kinase inhibitors of overexpressed FGFR1			R-HSA-2023462 (Reactome)
Tyrosine kinase inhibitors of FGFR1 fusion mutants			R-HSA-1839039 (Reactome)
	Ub-(Y55/Y227)p-SPRY2	Arrow	R-HSA-1295621 (Reactome)
	Ub-Activated FGFR1 complex:Ub-p-FRS2	Arrow	R-HSA-5654672 (Reactome)
	Ub:Y55/Y227-pSPRY2:CBL	Arrow	R-HSA-934604 (Reactome)
Ub:Y55/Y227-pSPRY2:CBL			R-HSA-1295621 (Reactome)
Ub			R-HSA-5654672 (Reactome)
Ub			R-HSA-934604 (Reactome)
	Y55/Y227-pSPRY2:CBL	Arrow	R-HSA-1295622 (Reactome)
Y55/Y227-pSPRY2:CBL			R-HSA-934604 (Reactome)
Y55/Y227-pSPRY2:CBL		mim-catalysis	R-HSA-934604 (Reactome)
	activated FGFR1:PLCG1	Arrow	R-HSA-5654167 (Reactome)
activated FGFR1:PLCG1			R-HSA-5654149 (Reactome)
activated FGFR1:PLCG1		mim-catalysis	R-HSA-5654149 (Reactome)
	activated FGFR1:p-4Y-PLCG1	Arrow	R-HSA-5654149 (Reactome)
activated FGFR1:p-4Y-PLCG1			R-HSA-5654165 (Reactome)
	p-4Y-PLCG1	Arrow	R-HSA-1839100 (Reactome)
	p-4Y-PLCG1	Arrow	R-HSA-5654165 (Reactome)
	p-FGFR1 fusion mutant dimers:PIK3R1	Arrow	R-HSA-1839078 (Reactome)
p-FGFR1 fusion mutant dimers:PIK3R1			R-HSA-1839080 (Reactome)
	p-FGFR1 fusion mutant dimers	Arrow	R-HSA-1839065 (Reactome)
p-FGFR1 fusion mutant dimers			R-HSA-1839078 (Reactome)
p-FGFR1 fusion mutant dimers		mim-catalysis	R-HSA-1839112 (Reactome)
	p-FGFR1 mutant fusions:PI3K	Arrow	R-HSA-1839080 (Reactome)
p-FGFR1 mutant fusions:PI3K		mim-catalysis	R-HSA-1839091 (Reactome)
p-MEK:ERK			R-HSA-1268210 (Reactome)
p-MEK:ERK		mim-catalysis	R-HSA-1268210 (Reactome)
	p-MEK:p-ERK	Arrow	R-HSA-1268210 (Reactome)
p-MEK:p-ERK			R-HSA-1268206 (Reactome)
	p-S111,S120-SPRY2	Arrow	R-HSA-1295604 (Reactome)
	p-STAT5	Arrow	R-HSA-1839112 (Reactome)
	p-T,Y MAPK dimers	Arrow	R-HSA-1295628 (Reactome)
p-T,Y MAPK dimers		Arrow	R-HSA-1295634 (Reactome)
p-T,Y MAPK dimers		mim-catalysis	R-HSA-5654560 (Reactome)
	p-T,Y MAPKs	Arrow	R-HSA-1268206 (Reactome)
p-T,Y MAPKs			R-HSA-1295628 (Reactome)
p-T250,T255,T385,S437-MKNK1		mim-catalysis	R-HSA-934559 (Reactome)
	p-Y177-BCR-pY-FGFR1 mutant:GRB2:p-GAB2:PIK3R1	Arrow	R-HSA-1839114 (Reactome)
p-Y177-BCR-pY-FGFR1 mutant:GRB2:p-GAB2:PIK3R1			R-HSA-1839102 (Reactome)
p-Y371-CBL:GRB2			R-HSA-5654673 (Reactome)
p21 RAS:GDP			R-HSA-5654392 (Reactome)
p21 RAS:GDP			R-HSA-5654600 (Reactome)
p21 RAS:GDP			R-HSA-5655326 (Reactome)
	p21 RAS:GTP	Arrow	R-HSA-5654392 (Reactome)
	p21 RAS:GTP	Arrow	R-HSA-5654600 (Reactome)
	p21 RAS:GTP	Arrow	R-HSA-5655326 (Reactome)
	pY-STAT1,3	Arrow	R-HSA-1888198 (Reactome)
	pY177-BCR-p-FGFR1 fusion mutant dimer	Arrow	R-HSA-1839067 (Reactome)
pY177-BCR-p-FGFR1 fusion mutant dimer			R-HSA-1839095 (Reactome)
	pY177-BCR-pY-FGFR1 mutant:GRB2:p-GAB1:PI3K	Arrow	R-HSA-1839102 (Reactome)
pY177-BCR-pY-FGFR1 mutant:GRB2:p-GAB1:PI3K		mim-catalysis	R-HSA-1839107 (Reactome)
	pY177-BCR-pY-FGFR1 mutant:GRB2:p-GAB2	Arrow	R-HSA-1839110 (Reactome)
pY177-BCR-pY-FGFR1 mutant:GRB2:p-GAB2			R-HSA-1839114 (Reactome)
	pY177-BCR1-p-FGFR1 mutant:GRB2:GAB2	Arrow	R-HSA-1839095 (Reactome)
pY177-BCR1-p-FGFR1 mutant:GRB2:GAB2			R-HSA-1839110 (Reactome)
pY177-BCR1-p-FGFR1 mutant:GRB2:GAB2		mim-catalysis	R-HSA-1839110 (Reactome)