Fc epsilon receptor (FCERI) signaling (Homo sapiens)

From WikiPathways

Description

Quality Tags

Ontology Terms

Bibliography

View all...

1. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
2. Turjanski AG, Vaqué JP, Gutkind JS.; ''MAP kinases and the control of nuclear events.''; PubMed Europe PMC Scholia
3. Yablonski D, Kadlecek T, Weiss A.; ''Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT.''; PubMed Europe PMC Scholia
4. Shen X, Li H, Ou Y, Tao W, Dong A, Kong J, Ji C, Yu S.; ''The secondary structure of calcineurin regulatory region and conformational change induced by calcium/calmodulin binding.''; PubMed Europe PMC Scholia
5. Reeve JL, Zou W, Liu Y, Maltzman JS, Ross FP, Teitelbaum SL.; ''SLP-76 couples Syk to the osteoclast cytoskeleton.''; PubMed Europe PMC Scholia
6. Bubeck Wardenburg J, Fu C, Jackman JK, Flotow H, Wilkinson SE, Williams DH, Johnson R, Kong G, Chan AC, Findell PR.; ''Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function.''; PubMed Europe PMC Scholia
7. Spencer E, Jiang J, Chen ZJ.; ''Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP.''; PubMed Europe PMC Scholia
8. Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE.; ''Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling.''; PubMed Europe PMC Scholia
9. Hendricks-Taylor LR, Motto DG, Zhang J, Siraganian RP, Koretzky GA.; ''SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells.''; PubMed Europe PMC Scholia
10. Bonizzi G, Karin M.; ''The two NF-kappaB activation pathways and their role in innate and adaptive immunity.''; PubMed Europe PMC Scholia
11. Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ, Wang RF.; ''NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways.''; PubMed Europe PMC Scholia
12. Liu SK, Fang N, Koretzky GA, McGlade CJ.; ''The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors.''; PubMed Europe PMC Scholia
13. Plotnikov A, Zehorai E, Procaccia S, Seger R.; ''The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.''; PubMed Europe PMC Scholia
14. Parrini MC, Lei M, Harrison SC, Mayer BJ.; ''Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1.''; PubMed Europe PMC Scholia
15. Young RM, Holowka D, Baird B.; ''A lipid raft environment enhances Lyn kinase activity by protecting the active site tyrosine from dephosphorylation.''; PubMed Europe PMC Scholia
16. Roberts PJ, Der CJ.; ''Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.''; PubMed Europe PMC Scholia
17. Tkaczyk C, Horejsi V, Iwaki S, Draber P, Samelson LE, Satterthwaite AB, Nahm DH, Metcalfe DD, Gilfillan AM.; ''NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation.''; PubMed Europe PMC Scholia
18. Manetz TS, Gonzalez-Espinosa C, Arudchandran R, Xirasagar S, Tybulewicz V, Rivera J.; ''Vav1 regulates phospholipase cgamma activation and calcium responses in mast cells.''; PubMed Europe PMC Scholia
19. Tybulewicz VL, Ardouin L, Prisco A, Reynolds LF.; ''Vav1: a key signal transducer downstream of the TCR.''; PubMed Europe PMC Scholia
20. Rusnak F, Mertz P.; ''Calcineurin: form and function.''; PubMed Europe PMC Scholia
21. Blank U, Rivera J.; ''The ins and outs of IgE-dependent mast-cell exocytosis.''; PubMed Europe PMC Scholia
22. Lu W, Mayer BJ.; ''Mechanism of activation of Pak1 kinase by membrane localization.''; PubMed Europe PMC Scholia
23. Latres E, Chiaur DS, Pagano M.; ''The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin.''; PubMed Europe PMC Scholia
24. Krappmann D, Hatada EN, Tegethoff S, Li J, Klippel A, Giese K, Baeuerle PA, Scheidereit C.; ''The I kappa B kinase (IKK) complex is tripartite and contains IKK gamma but not IKAP as a regular component.''; PubMed Europe PMC Scholia
25. Häcker H, Karin M.; ''Regulation and function of IKK and IKK-related kinases.''; PubMed Europe PMC Scholia
26. Cuenda A, Dorow DS.; ''Differential activation of stress-activated protein kinase kinases SKK4/MKK7 and SKK1/MKK4 by the mixed-lineage kinase-2 and mitogen-activated protein kinase kinase (MKK) kinase-1.''; PubMed Europe PMC Scholia
27. Matsuda M, Paterson HF, Rodriguez R, Fensome AC, Ellis MV, Swann K, Katan M.; ''Real time fluorescence imaging of PLC gamma translocation and its interaction with the epidermal growth factor receptor.''; PubMed Europe PMC Scholia
28. Loh C, Shaw KT, Carew J, Viola JP, Luo C, Perrino BA, Rao A.; ''Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity.''; PubMed Europe PMC Scholia
29. DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M.; ''A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB.''; PubMed Europe PMC Scholia
30. Roskoski R.; ''ERK1/2 MAP kinases: structure, function, and regulation.''; PubMed Europe PMC Scholia
31. Peng Q, Malhotra S, Torchia JA, Kerr WG, Coggeshall KM, Humphrey MB.; ''TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1.''; PubMed Europe PMC Scholia
32. Gross BS, Lee JR, Clements JL, Turner M, Tybulewicz VL, Findell PR, Koretzky GA, Watson SP.; ''Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets.''; PubMed Europe PMC Scholia
33. Wellbrock C, Karasarides M, Marais R.; ''The RAF proteins take centre stage.''; PubMed Europe PMC Scholia
34. Nishida K, Yamasaki S, Hasegawa A, Iwamatsu A, Koseki H, Hirano T.; ''Gab2, via PI-3K, regulates ARF1 in FcεRI-mediated granule translocation and mast cell degranulation.''; PubMed Europe PMC Scholia
35. Dong W, Liu Y, Peng J, Chen L, Zou T, Xiao H, Liu Z, Li W, Bu Y, Qi Y.; ''The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4.''; PubMed Europe PMC Scholia
36. Brown MD, Sacks DB.; ''Protein scaffolds in MAP kinase signalling.''; PubMed Europe PMC Scholia
37. Davis RJ.; ''MAPKs: new JNK expands the group.''; PubMed Europe PMC Scholia
38. Song JS, Haleem-Smith H, Arudchandran R, Gomez J, Scott PM, Mill JF, Tan TH, Rivera J.; ''Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway.''; PubMed Europe PMC Scholia
39. Altman A, Villalba M.; ''Protein kinase C-theta (PKC theta): a key enzyme in T cell life and death.''; PubMed Europe PMC Scholia
40. Kroll M, Conconi M, Desterro MJ, Marin A, Thomas D, Friguet B, Hay RT, Virelizier JL, Arenzana-Seisdedos F, Rodriguez MS.; ''The carboxy-terminus of I kappaB alpha determines susceptibility to degradation by the catalytic core of the proteasome.''; PubMed Europe PMC Scholia
41. Alvarez-Errico D, Lessmann E, Rivera J.; ''Adapters in the organization of mast cell signaling.''; PubMed Europe PMC Scholia
42. Dennler S, Prunier C, Ferrand N, Gauthier JM, Atfi A.; ''c-Jun inhibits transforming growth factor beta-mediated transcription by repressing Smad3 transcriptional activity.''; PubMed Europe PMC Scholia
43. Cseh B, Doma E, Baccarini M.; ''"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.''; PubMed Europe PMC Scholia
44. Qiu L, Dhe-Paganon S.; ''Oligomeric structure of the MALT1 tandem Ig-like domains.''; PubMed Europe PMC Scholia
45. Alkalay I, Yaron A, Hatzubai A, Orian A, Ciechanover A, Ben-Neriah Y.; ''Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway.''; PubMed Europe PMC Scholia
46. Jabril-Cuenod B, Zhang C, Scharenberg AM, Paolini R, Numerof R, Beaven MA, Kinet JP.; ''Syk-dependent phosphorylation of Shc. A potential link between FcepsilonRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2.''; PubMed Europe PMC Scholia
47. Iwaki S, Spicka J, Tkaczyk C, Jensen BM, Furumoto Y, Charles N, Kovarova M, Rivera J, Horejsi V, Metcalfe DD, Gilfillan AM.; ''Kit- and Fc epsilonRI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cells.''; PubMed Europe PMC Scholia
48. 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
49. Sato S, Sanjo H, Takeda K, Ninomiya-Tsuji J, Yamamoto M, Kawai T, Matsumoto K, Takeuchi O, Akira S.; ''Essential function for the kinase TAK1 in innate and adaptive immune responses.''; PubMed Europe PMC Scholia
50. Melowic HR, Stahelin RV, Blatner NR, Tian W, Hayashi K, Altman A, Cho W.; ''Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Ctheta.''; PubMed Europe PMC Scholia
51. Okazaki K, Sagata N.; ''The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells.''; PubMed Europe PMC Scholia
52. Lennartsson J, Blume-Jensen P, Hermanson M, Pontén E, Carlberg M, Rönnstrand L.; ''Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction.''; PubMed Europe PMC Scholia
53. Wang X, Chuang HC, Li JP, Tan TH.; ''Regulation of PKC-θ function by phosphorylation in T cell receptor signaling.''; PubMed Europe PMC Scholia
54. Chong C, Tan L, Lim L, Manser E.; ''The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity.''; PubMed Europe PMC Scholia
55. Siraganian RP.; ''Mast cell signal transduction from the high-affinity IgE receptor.''; PubMed Europe PMC Scholia
56. Hayden MS, Ghosh S.; ''Signaling to NF-kappaB.''; PubMed Europe PMC Scholia
57. Oeckinghaus A, Wegener E, Welteke V, Ferch U, Arslan SC, Ruland J, Scheidereit C, Krappmann D.; ''Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation.''; PubMed Europe PMC Scholia
58. Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A.; ''Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells.''; PubMed Europe PMC Scholia
59. Nore BF, Mattsson PT, Antonsson P, Bäckesjö CM, Westlund A, Lennartsson J, Hansson H, Löw P, Rönnstrand L, Smith CI.; ''Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases.''; PubMed Europe PMC Scholia
60. Lamothe B, Besse A, Campos AD, Webster WK, Wu H, Darnay BG.; ''Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation.''; PubMed Europe PMC Scholia
61. Sun L, Deng L, Ea CK, Xia ZP, Chen ZJ.; ''The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes.''; PubMed Europe PMC Scholia
62. Deacon K, Blank JL.; ''Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo.''; PubMed Europe PMC Scholia
63. 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
64. Zhao ZS, Manser E.; ''PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation.''; PubMed Europe PMC Scholia
65. Vanhaesebroeck B, Alessi DR.; ''The PI3K-PDK1 connection: more than just a road to PKB.''; PubMed Europe PMC Scholia
66. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC Scholia
67. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ.; ''TAK1 is a ubiquitin-dependent kinase of MKK and IKK.''; PubMed Europe PMC Scholia
68. Wu J, Motto DG, Koretzky GA, Weiss A.; ''Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation.''; PubMed Europe PMC Scholia
69. Chen TY, Illing M, Molday LL, Hsu YT, Yau KW, Molday RS.; ''Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.''; PubMed Europe PMC Scholia
70. Kim YJ, Sekiya F, Poulin B, Bae YS, Rhee SG.; ''Mechanism of B-cell receptor-induced phosphorylation and activation of phospholipase C-gamma2.''; PubMed Europe PMC Scholia
71. Park H, Wahl MI, Afar DE, Turck CW, Rawlings DJ, Tam C, Scharenberg AM, Kinet JP, Witte ON.; ''Regulation of Btk function by a major autophosphorylation site within the SH3 domain.''; PubMed Europe PMC Scholia
72. Liu Y, Graham C, Li A, Fisher RJ, Shaw S.; ''Phosphorylation of the protein kinase C-theta activation loop and hydrophobic motif regulates its kinase activity, but only activation loop phosphorylation is critical to in vivo nuclear-factor-kappaB induction.''; PubMed Europe PMC Scholia
73. Rhee SG.; ''Regulation of phosphoinositide-specific phospholipase C.''; PubMed Europe PMC Scholia
74. Holowka D, Sil D, Torigoe C, Baird B.; ''Insights into immunoglobulin E receptor signaling from structurally defined ligands.''; PubMed Europe PMC Scholia
75. Carter RS, Geyer BC, Xie M, Acevedo-Suárez CA, Ballard DW.; ''Persistent activation of NF-kappa B by the tax transforming protein involves chronic phosphorylation of IkappaB kinase subunits IKKbeta and IKKgamma.''; PubMed Europe PMC Scholia
76. Garman SC, Wurzburg BA, Tarchevskaya SS, Kinet JP, Jardetzky TS.; ''Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha.''; PubMed Europe PMC Scholia
77. Shiue L, Green J, Green OM, Karas JL, Morgenstern JP, Ram MK, Taylor MK, Zoller MJ, Zydowsky LD, Bolen JB.; ''Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI.''; PubMed Europe PMC Scholia
78. Donella-Deana A, Cesaro L, Ruzzene M, Brunati AM, Marin O, Pinna LA.; ''Spontaneous autophosphorylation of Lyn tyrosine kinase at both its activation segment and C-terminal tail confers altered substrate specificity.''; PubMed Europe PMC Scholia
79. Kishimoto K, Matsumoto K, Ninomiya-Tsuji J.; ''TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop.''; PubMed Europe PMC Scholia
80. Gilmore TD.; ''Introduction to NF-kappaB: players, pathways, perspectives.''; PubMed Europe PMC Scholia
81. Jiang Y, Cheng H.; ''Evidence of LAT as a dual substrate for Lck and Syk in T lymphocytes.''; PubMed Europe PMC Scholia
82. Kanayama A, Seth RB, Sun L, Ea CK, Hong M, Shaito A, Chiu YH, Deng L, Chen ZJ.; ''TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains.''; PubMed Europe PMC Scholia
83. Thuille N, Heit I, Fresser F, Krumböck N, Bauer B, Leuthaeusser S, Dammeier S, Graham C, Copeland TD, Shaw S, Baier G.; ''Critical role of novel Thr-219 autophosphorylation for the cellular function of PKCtheta in T lymphocytes.''; PubMed Europe PMC Scholia
84. Bos JL, Rehmann H, Wittinghofer A.; ''GEFs and GAPs: critical elements in the control of small G proteins.''; PubMed Europe PMC Scholia
85. Jevremovic D, Billadeau DD, Schoon RA, Dick CJ, Irvin BJ, Zhang W, Samelson LE, Abraham RT, Leibson PJ.; ''Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity.''; PubMed Europe PMC Scholia
86. Hogan PG, Chen L, Nardone J, Rao A.; ''Transcriptional regulation by calcium, calcineurin, and NFAT.''; PubMed Europe PMC Scholia
87. Dinh M, Grunberger D, Ho H, Tsing SY, Shaw D, Lee S, Barnett J, Hill RJ, Swinney DC, Bradshaw JM.; ''Activation mechanism and steady state kinetics of Bruton's tyrosine kinase.''; PubMed Europe PMC Scholia
88. Baldi L, Brown K, Franzoso G, Siebenlist U.; ''Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated proteolysis of I kappa B-alpha.''; PubMed Europe PMC Scholia
89. Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
90. Carter RS, Pennington KN, Ungurait BJ, Arrate P, Ballard DW.; ''Signal-induced ubiquitination of I kappaB Kinase-beta.''; PubMed Europe PMC Scholia
91. Mizukami Y, Yoshioka K, Morimoto S, Yoshida Ki.; ''A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion.''; PubMed Europe PMC Scholia
92. Parrini MC, Camonis J, Matsuda M, de Gunzburg J.; ''Dissecting activation of the PAK1 kinase at protrusions in living cells.''; PubMed Europe PMC Scholia
93. Yu M, Lowell CA, Neel BG, Gu H.; ''Scaffolding adapter Grb2-associated binder 2 requires Syk to transmit signals from FcepsilonRI.''; PubMed Europe PMC Scholia
94. Aghazadeh B, Lowry WE, Huang XY, Rosen MK.; ''Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation.''; PubMed Europe PMC Scholia
95. 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
96. Rothwarf DM, Zandi E, Natoli G, Karin M.; ''IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex.''; PubMed Europe PMC Scholia
97. Vonakis BM, Chen H, Haleem-Smith H, Metzger H.; ''The unique domain as the site on Lyn kinase for its constitutive association with the high affinity receptor for IgE.''; PubMed Europe PMC Scholia
98. Park S, Uesugi M, Verdine GL.; ''A second calcineurin binding site on the NFAT regulatory domain.''; PubMed Europe PMC Scholia
99. Tanner MJ, Hanel W, Gaffen SL, Lin X.; ''CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation.''; PubMed Europe PMC Scholia
100. Harmer SL, DeFranco AL.; ''Shc contains two Grb2 binding sites needed for efficient formation of complexes with SOS in B lymphocytes.''; PubMed Europe PMC Scholia
101. Murphy LO, Smith S, Chen RH, Fingar DC, Blenis J.; ''Molecular interpretation of ERK signal duration by immediate early gene products.''; PubMed Europe PMC Scholia
102. Shambharkar PB, Blonska M, Pappu BP, Li H, You Y, Sakurai H, Darnay BG, Hara H, Penninger J, Lin X.; ''Phosphorylation and ubiquitination of the IkappaB kinase complex by two distinct signaling pathways.''; PubMed Europe PMC Scholia
103. Raivich G.; ''c-Jun expression, activation and function in neural cell death, inflammation and repair.''; PubMed Europe PMC Scholia
104. Adhikari A, Xu M, Chen ZJ.; ''Ubiquitin-mediated activation of TAK1 and IKK.''; PubMed Europe PMC Scholia
105. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
106. Teramoto H, Salem P, Robbins KC, Bustelo XR, Gutkind JS.; ''Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Rac1-JNK pathway.''; PubMed Europe PMC Scholia
107. Okamura H, Aramburu J, García-Rodríguez C, Viola JP, Raghavan A, Tahiliani M, Zhang X, Qin J, Hogan PG, Rao A.; ''Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity.''; PubMed Europe PMC Scholia
108. Whitman M, Downes CP, Keeler M, Keller T, Cantley L.; ''Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate.''; PubMed Europe PMC Scholia
109. Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J.; ''The structural basis of the activation of Ras by Sos.''; PubMed Europe PMC Scholia
110. Allen JD, Jaffer ZM, Park SJ, Burgin S, Hofmann C, Sells MA, Chen S, Derr-Yellin E, Michels EG, McDaniel A, Bessler WK, Ingram DA, Atkinson SJ, Travers JB, Chernoff J, Clapp DW.; ''p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics.''; PubMed Europe PMC Scholia
111. Manicassamy S, Gupta S, Sun Z.; ''Selective function of PKC-theta in T cells.''; PubMed Europe PMC Scholia
112. Rueda D, Thome M.; ''Phosphorylation of CARMA1: the link(er) to NF-kappaB activation.''; PubMed Europe PMC Scholia
113. McKay MM, Morrison DK.; ''Integrating signals from RTKs to ERK/MAPK.''; PubMed Europe PMC Scholia
114. Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, Takeshita T, Tsuchiya S, Konno T, Sugamura K.; ''Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT.''; PubMed Europe PMC Scholia
115. Wen R, Jou ST, Chen Y, Hoffmeyer A, Wang D.; ''Phospholipase C gamma 2 is essential for specific functions of Fc epsilon R and Fc gamma R.''; PubMed Europe PMC Scholia
116. Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM.; ''Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma.''; PubMed Europe PMC Scholia
117. Sakurai H, Miyoshi H, Mizukami J, Sugita T.; ''Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1.''; PubMed Europe PMC Scholia
118. Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR, Templeton DJ.; ''Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1.''; PubMed Europe PMC Scholia
119. Deckert M, Tartare-Deckert S, Couture C, Mustelin T, Altman A.; ''Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product.''; PubMed Europe PMC Scholia
120. Kovárová M, Tolar P, Arudchandran R, Dráberová L, Rivera J, Dráber P.; ''Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fcepsilon receptor I aggregation.''; PubMed Europe PMC Scholia
121. Glover JN, Harrison SC.; ''Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA.''; PubMed Europe PMC Scholia
122. Pribluda VS, Pribluda C, Metzger H.; ''Transphosphorylation as the mechanism by which the high-affinity receptor for IgE is phosphorylated upon aggregation.''; PubMed Europe PMC Scholia
123. Sebban-Benin H, Pescatore A, Fusco F, Pascuale V, Gautheron J, Yamaoka S, Moncla A, Ursini MV, Courtois G.; ''Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti.''; PubMed Europe PMC Scholia
124. Takeuchi K, Roehrl MH, Sun ZY, Wagner G.; ''Structure of the calcineurin-NFAT complex: defining a T cell activation switch using solution NMR and crystal coordinates.''; PubMed Europe PMC Scholia
125. Yang YJ, Chen W, Carrigan SO, Chen WM, Roth K, Akiyama T, Inoue J, Marshall JS, Berman JN, Lin TJ.; ''TRAF6 specifically contributes to FcepsilonRI-mediated cytokine production but not mast cell degranulation.''; PubMed Europe PMC Scholia
126. Kyriakis JM, Avruch J.; ''Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.''; PubMed Europe PMC Scholia
127. Dráber P, Dráberová L.; ''Lipid rafts in mast cell signaling.''; PubMed Europe PMC Scholia
128. Lutz C, Nimpf J, Jenny M, Boecklinger K, Enzinger C, Utermann G, Baier-Bitterlich G, Baier G.; ''Evidence of functional modulation of the MEKK/JNK/cJun signaling cascade by the low density lipoprotein receptor-related protein (LRP).''; PubMed Europe PMC Scholia
129. Cargnello M, Roux PP.; ''Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.''; PubMed Europe PMC Scholia
130. Thome M, Charton JE, Pelzer C, Hailfinger S.; ''Antigen receptor signaling to NF-kappaB via CARMA1, BCL10, and MALT1.''; PubMed Europe PMC Scholia
131. Liu Y, Graham C, Parravicini V, Brown MJ, Rivera J, Shaw S.; ''Protein kinase C theta is expressed in mast cells and is functionally involved in Fcepsilon receptor I signaling.''; PubMed Europe PMC Scholia
132. Besse A, Lamothe B, Campos AD, Webster WK, Maddineni U, Lin SC, Wu H, Darnay BG.; ''TAK1-dependent signaling requires functional interaction with TAB2/TAB3.''; PubMed Europe PMC Scholia
133. Kihara H, Siraganian RP.; ''Src homology 2 domains of Syk and Lyn bind to tyrosine-phosphorylated subunits of the high affinity IgE receptor.''; PubMed Europe PMC Scholia
134. Luo C, Shaw KT, Raghavan A, Aramburu J, Garcia-Cozar F, Perrino BA, Hogan PG, Rao A.; ''Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import.''; PubMed Europe PMC Scholia
135. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
136. Rawlings DJ, Scharenberg AM, Park H, Wahl MI, Lin S, Kato RM, Fluckiger AC, Witte ON, Kinet JP.; ''Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases.''; PubMed Europe PMC Scholia
137. Sundarrajan M, Boyle DL, Chabaud-Riou M, Hammaker D, Firestein GS.; ''Expression of the MAPK kinases MKK-4 and MKK-7 in rheumatoid arthritis and their role as key regulators of JNK.''; PubMed Europe PMC Scholia
138. Israël A.; ''The IKK complex, a central regulator of NF-kappaB activation.''; PubMed Europe PMC Scholia
139. Kimura T, Kihara H, Bhattacharyya S, Sakamoto H, Appella E, Siraganian RP.; ''Downstream signaling molecules bind to different phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) peptides of the high affinity IgE receptor.''; PubMed Europe PMC Scholia
140. Nishida K, Yoshida Y, Itoh M, Fukada T, Ohtani T, Shirogane T, Atsumi T, Takahashi-Tezuka M, Ishihara K, Hibi M, Hirano T.; ''Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors.''; PubMed Europe PMC Scholia
141. Kim HL, Vander Griend DJ, Yang X, Benson DA, Dubauskas Z, Yoshida BA, Chekmareva MA, Ichikawa Y, Sokoloff MH, Zhan P, Karrison T, Lin A, Stadler WM, Ichikawa T, Rubin MA, Rinker-Schaeffer CW.; ''Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers.''; PubMed Europe PMC Scholia
142. Kawakami Y, Yao L, Miura T, Tsukada S, Witte ON, Kawakami T.; ''Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking.''; PubMed Europe PMC Scholia
143. Matsumoto R, Wang D, Blonska M, Li H, Kobayashi M, Pappu B, Chen Y, Wang D, Lin X.; ''Phosphorylation of CARMA1 plays a critical role in T Cell receptor-mediated NF-kappaB activation.''; PubMed Europe PMC Scholia
144. Koyasu S.; ''The role of PI3K in immune cells.''; PubMed Europe PMC Scholia
145. Wu LC.; ''Immunoglobulin E receptor signaling and asthma.''; PubMed Europe PMC Scholia
146. Chen ZJ, Parent L, Maniatis T.; ''Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity.''; PubMed Europe PMC Scholia
147. Wang X, Nadarajah B, Robinson AC, McColl BW, Jin JW, Dajas-Bailador F, Boot-Handford RP, Tournier C.; ''Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in the nervous system causes severe brain developmental defects and premature death.''; PubMed Europe PMC Scholia
148. Ainbinder E, Bergelson S, Pinkus R, Daniel V.; ''Regulatory mechanisms involved in activator-protein-1 (AP-1)-mediated activation of glutathione-S-transferase gene expression by chemical agents.''; PubMed Europe PMC Scholia
149. Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K.; ''TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway.''; PubMed Europe PMC Scholia

History

View all...

Compare	Revision	Action	Time	User	Comment
	114731	view	16:21, 25 January 2021	ReactomeTeam	Reactome version 75
	113175	view	11:24, 2 November 2020	ReactomeTeam	Reactome version 74
	112403	view	15:34, 9 October 2020	ReactomeTeam	Reactome version 73
	101307	view	11:19, 1 November 2018	ReactomeTeam	reactome version 66
	100844	view	20:51, 31 October 2018	ReactomeTeam	reactome version 65
	100385	view	19:25, 31 October 2018	ReactomeTeam	reactome version 64
	99932	view	16:09, 31 October 2018	ReactomeTeam	reactome version 63
	99487	view	14:41, 31 October 2018	ReactomeTeam	reactome version 62 (2nd attempt)
	99139	view	12:40, 31 October 2018	ReactomeTeam	reactome version 62
	93828	view	13:39, 16 August 2017	ReactomeTeam	reactome version 61
	93378	view	11:22, 9 August 2017	ReactomeTeam	reactome version 61
	87447	view	13:46, 22 July 2016	Mkutmon	Ontology Term : 'Fc epsilon receptor mediated signaling pathway' added !
	86464	view	09:18, 11 July 2016	ReactomeTeam	reactome version 56
	83375	view	11:03, 18 November 2015	ReactomeTeam	Version54
	81548	view	13:05, 21 August 2015	ReactomeTeam	Version53
	77017	view	08:31, 17 July 2014	ReactomeTeam	Fixed remaining interactions
	76722	view	12:08, 16 July 2014	ReactomeTeam	Fixed remaining interactions
	76048	view	10:10, 11 June 2014	ReactomeTeam	Re-fixing comment source
	75757	view	11:25, 10 June 2014	ReactomeTeam	Reactome 48 Update
	75107	view	14:05, 8 May 2014	Anwesha	Fixing comment source for displaying WikiPathways description
	74754	view	08:50, 30 April 2014	ReactomeTeam	New pathway

External references

DataNodes

View all...

Name	Type	Database reference	Comment
ADP	Metabolite	CHEBI:16761 (ChEBI)
AMP	Metabolite	CHEBI:16027 (ChEBI)
ATP	Metabolite	CHEBI:15422 (ChEBI)
Active Calmodulin	Complex	REACT_3178 (Reactome)
Allergin:p-LYN:p-FCERI:IgE aggregate	Complex	REACT_165244 (Reactome)
Allergin		REACT_164121 (Reactome)
BCL10 [cytosol]	Protein	O95999 (Uniprot-TrEMBL)
BCL10:MALT1	Complex	REACT_165506 (Reactome)
BCL10	Protein	O95999 (Uniprot-TrEMBL)
CALM1 [cytosol]	Protein	P62158 (Uniprot-TrEMBL)
CALM1 [nucleoplasm]	Protein	P62158 (Uniprot-TrEMBL)
CALM1	Protein	P62158 (Uniprot-TrEMBL)
CARD11(1-1147)	Protein	Q9BXL7 (Uniprot-TrEMBL)
CHUK [cytosol]	Protein	O15111 (Uniprot-TrEMBL)
Ca2+ [cytosol]	Metabolite	CHEBI:29108 (ChEBI)
Ca2+ [nucleoplasm]	Metabolite	CHEBI:29108 (ChEBI)
Ca2+	Metabolite	CHEBI:29108 (ChEBI)
Calcineurin (CaN)	Complex	REACT_119672 (Reactome)
Calcineurin:Calmodulin (CaN:CaM)	Complex	REACT_119482 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:SYK	Complex	REACT_165178 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:p-6Y-SYK	Complex	REACT_165068 (Reactome)
DAG:p-5Y-PKC-theta:CBM complex	Complex	REACT_165355 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:TRAF6 oligomer	Complex	REACT_164024 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:TRAF6	Complex	REACT_164811 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:TAK1:TAB1:TAB2/3	Complex	REACT_165256 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:activated TAK1 complex	Complex	REACT_164823 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6	Complex	REACT_165243 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer	Complex	REACT_165009 (Reactome)
DAG:p-5Y-PKC-theta:p-S552,S645-CARMA1 oligomer	Complex	REACT_164911 (Reactome)
DAG:p-5Y-PKC-theta:p-S552,S645-CARMA1	Complex	REACT_164769 (Reactome)
DAGs [plasma membrane]	Metabolite	CHEBI:18035 (ChEBI)
DAGs	Metabolite	CHEBI:18035 (ChEBI)
FCER1A [plasma membrane]	Protein	P12319 (Uniprot-TrEMBL)
FCER1G [plasma membrane]	Protein	P30273 (Uniprot-TrEMBL)
FCERI:IgE:allergin aggregate	Complex	REACT_164529 (Reactome)
FCERI:IgE	Complex	REACT_164240 (Reactome)
FOS	Protein	P01100 (Uniprot-TrEMBL)
Fe3+ [cytosol]	Metabolite	CHEBI:29034 (ChEBI)
Fe3+ [nucleoplasm]	Metabolite	CHEBI:29034 (ChEBI)
GAB2 [cytosol]	Protein	Q9UQC2 (Uniprot-TrEMBL)
GAB2	Protein	Q9UQC2 (Uniprot-TrEMBL)
GADS:SLP76	Complex	REACT_147999 (Reactome)
GDP [cytosol]	Metabolite	CHEBI:17552 (ChEBI)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GRAP2 [cytosol]	Protein	O75791 (Uniprot-TrEMBL)
GRB2-1 [cytosol]	Protein	P62993-1 (Uniprot-TrEMBL)
GRB2:SOS1	Complex	REACT_4435 (Reactome)
GTP [cytosol]	Metabolite	CHEBI:15996 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
H2O	Metabolite	CHEBI:15377 (ChEBI)
HRAS(1-186) [plasma membrane]	Protein	P01112 (Uniprot-TrEMBL)
I(1,4,5)P3 [cytosol]	Metabolite	CHEBI:16595 (ChEBI)
I(1,4,5)P3	Metabolite	CHEBI:16595 (ChEBI)
IGHE(1-428) [extracellular region]	Protein	P01854 (Uniprot-TrEMBL)
IGHV(1-?) [extracellular region]	Protein	A2KUC3 (Uniprot-TrEMBL)
IGHV7-81(1-?) [extracellular region]	Protein	Q6PIL0 (Uniprot-TrEMBL)
IGKC(1-106) [extracellular region]	Protein	P01834 (Uniprot-TrEMBL)
IGKV1-5(23-?) [extracellular region]	Protein	P01602 (Uniprot-TrEMBL)
IGKV4-1(21-?) [extracellular region]	Protein	P06312 (Uniprot-TrEMBL)
IGKVA18(21-?) [extracellular region]	Protein	A2NJV5 (Uniprot-TrEMBL)
IGLC1(1-105) [extracellular region]	Protein	P0CG04 (Uniprot-TrEMBL)
IGLC2(?-106) [extracellular region]	Protein	P0CG05 (Uniprot-TrEMBL)
IGLC3(?-106) [extracellular region]	Protein	P0CG06 (Uniprot-TrEMBL)
IGLC6(?-106) [extracellular region]	Protein	P0CF74 (Uniprot-TrEMBL)
IGLC7(?-106) [extracellular region]	Protein	A0M8Q6 (Uniprot-TrEMBL)
IGLV(23-?) [extracellular region]	Protein	A2NXD2 (Uniprot-TrEMBL)
IGLV1-36(1-?) [extracellular region]	Protein	Q5NV67 (Uniprot-TrEMBL)
IGLV1-40(1-?) [extracellular region]	Protein	Q5NV69 (Uniprot-TrEMBL)
IGLV1-44(1-?) [extracellular region]	Protein	Q5NV81 (Uniprot-TrEMBL)
IGLV10-54(1-?) [extracellular region]	Protein	Q5NV86 (Uniprot-TrEMBL)
IGLV11-55(1-?) [extracellular region]	Protein	Q5NV87 (Uniprot-TrEMBL)
IGLV2-11(1-?) [extracellular region]	Protein	Q5NV84 (Uniprot-TrEMBL)
IGLV2-18(1-?) [extracellular region]	Protein	Q5NV65 (Uniprot-TrEMBL)
IGLV2-23(1-?) [extracellular region]	Protein	Q5NV89 (Uniprot-TrEMBL)
IGLV2-33(1-?) [extracellular region]	Protein	Q5NV66 (Uniprot-TrEMBL)
IGLV3-12(1-?) [extracellular region]	Protein	Q5NV85 (Uniprot-TrEMBL)
IGLV3-16(1-?) [extracellular region]	Protein	Q5NV64 (Uniprot-TrEMBL)
IGLV3-22(1-?) [extracellular region]	Protein	Q5NV75 (Uniprot-TrEMBL)
IGLV3-25(1-?) [extracellular region]	Protein	Q5NV90 (Uniprot-TrEMBL)
IGLV3-27(1-?) [extracellular region]	Protein	Q5NV91 (Uniprot-TrEMBL)
IGLV4-3(1-?) [extracellular region]	Protein	Q5NV61 (Uniprot-TrEMBL)
IGLV4-60(1-?) [extracellular region]	Protein	Q5NV79 (Uniprot-TrEMBL)
IGLV4-69(1-?) [extracellular region]	Protein	Q5NV92 (Uniprot-TrEMBL)
IGLV5-37(1-?) [extracellular region]	Protein	Q5NV68 (Uniprot-TrEMBL)
IGLV5-45(1-?) [extracellular region]	Protein	Q5NV82 (Uniprot-TrEMBL)
IGLV7-43(1-?) [extracellular region]	Protein	Q5NV80 (Uniprot-TrEMBL)
IGLV7-46(1-?) [extracellular region]	Protein	Q5NV83 (Uniprot-TrEMBL)
IGLV8-61(1-?) [extracellular region]	Protein	Q5NV62 (Uniprot-TrEMBL)
IKBKB [cytosol]	Protein	O14920 (Uniprot-TrEMBL)
IKBKG [cytosol]	Protein	Q9Y6K9 (Uniprot-TrEMBL)
IKKA:IKKB:NEMO	Complex	REACT_7693 (Reactome)
IP3 receptor homotetramer	Complex	REACT_12247 (Reactome)
IP3 receptor:IP3 complex	Complex	REACT_12249 (Reactome)
ITPR1 [endoplasmic reticulum membrane]	Protein	Q14643 (Uniprot-TrEMBL)
ITPR2 [endoplasmic reticulum membrane]	Protein	Q14571 (Uniprot-TrEMBL)
ITPR3 [endoplasmic reticulum membrane]	Protein	Q14573 (Uniprot-TrEMBL)
Ig heavy chain V-I region EU [extracellular region]	Protein	P01742 (Uniprot-TrEMBL)
Ig heavy chain V-I region HG3 [extracellular region]	Protein	P01743 (Uniprot-TrEMBL)
Ig heavy chain V-I region Mot [extracellular region]	Protein	P06326 (Uniprot-TrEMBL)
Ig heavy chain V-I region ND [extracellular region]	Protein	P01744 (Uniprot-TrEMBL)
Ig heavy chain V-I region SIE [extracellular region]	Protein	P01761 (Uniprot-TrEMBL)
Ig heavy chain V-I region WOL [extracellular region]	Protein	P01760 (Uniprot-TrEMBL)
Ig heavy chain V-II region ARH-77 [extracellular region]	Protein	P06331 (Uniprot-TrEMBL)
Ig heavy chain V-II region COR [extracellular region]	Protein	P01815 (Uniprot-TrEMBL)
Ig heavy chain V-II region DAW [extracellular region]	Protein	P01816 (Uniprot-TrEMBL)
Ig heavy chain V-II region HE [extracellular region]	Protein	P01818 (Uniprot-TrEMBL)
Ig heavy chain V-II region MCE [extracellular region]	Protein	P01817 (Uniprot-TrEMBL)
Ig heavy chain V-II region NEWM [extracellular region]	Protein	P01825 (Uniprot-TrEMBL)
Ig heavy chain V-II region OU [extracellular region]	Protein	P01814 (Uniprot-TrEMBL)
Ig heavy chain V-II region SESS [extracellular region]	Protein	P04438 (Uniprot-TrEMBL)
Ig heavy chain V-II region WAH [extracellular region]	Protein	P01824 (Uniprot-TrEMBL)
Ig heavy chain V-III region BRO [extracellular region]	Protein	P01766 (Uniprot-TrEMBL)
Ig heavy chain V-III region BUR [extracellular region]	Protein	P01773 (Uniprot-TrEMBL)
Ig heavy chain V-III region BUT [extracellular region]	Protein	P01767 (Uniprot-TrEMBL)
Ig heavy chain V-III region CAM [extracellular region]	Protein	P01768 (Uniprot-TrEMBL)
Ig heavy chain V-III region DOB [extracellular region]	Protein	P01782 (Uniprot-TrEMBL)
Ig heavy chain V-III region GA [extracellular region]	Protein	P01769 (Uniprot-TrEMBL)
Ig heavy chain V-III region GAL [extracellular region]	Protein	P01781 (Uniprot-TrEMBL)
Ig heavy chain V-III region HIL [extracellular region]	Protein	P01771 (Uniprot-TrEMBL)
Ig heavy chain V-III region JON [extracellular region]	Protein	P01780 (Uniprot-TrEMBL)
Ig heavy chain V-III region KOL [extracellular region]	Protein	P01772 (Uniprot-TrEMBL)
Ig heavy chain V-III region LAY [extracellular region]	Protein	P01775 (Uniprot-TrEMBL)
Ig heavy chain V-III region NIE [extracellular region]	Protein	P01770 (Uniprot-TrEMBL)
Ig heavy chain V-III region POM [extracellular region]	Protein	P01774 (Uniprot-TrEMBL)
Ig heavy chain V-III region TEI [extracellular region]	Protein	P01777 (Uniprot-TrEMBL)
Ig heavy chain V-III region TIL [extracellular region]	Protein	P01765 (Uniprot-TrEMBL)
Ig heavy chain V-III region TRO [extracellular region]	Protein	P01762 (Uniprot-TrEMBL)
Ig heavy chain V-III region TUR [extracellular region]	Protein	P01779 (Uniprot-TrEMBL)
Ig heavy chain V-III region WAS [extracellular region]	Protein	P01776 (Uniprot-TrEMBL)
Ig heavy chain V-III region WEA [extracellular region]	Protein	P01763 (Uniprot-TrEMBL)
Ig heavy chain V-III region ZAP [extracellular region]	Protein	P01778 (Uniprot-TrEMBL)
Ig kappa chain V region EV15 [extracellular region]	Protein	P06315 (Uniprot-TrEMBL)
Ig kappa chain V-I region AG [extracellular region]	Protein	P01593 (Uniprot-TrEMBL)
Ig kappa chain V-I region AU [extracellular region]	Protein	P01594 (Uniprot-TrEMBL)
Ig kappa chain V-I region BAN [extracellular region]	Protein	P04430 (Uniprot-TrEMBL)
Ig kappa chain V-I region Bi [extracellular region]	Protein	P01595 (Uniprot-TrEMBL)
Ig kappa chain V-I region CAR [extracellular region]	Protein	P01596 (Uniprot-TrEMBL)
Ig kappa chain V-I region DEE [extracellular region]	Protein	P01597 (Uniprot-TrEMBL)
Ig kappa chain V-I region Daudi [extracellular region]	Protein	P04432 (Uniprot-TrEMBL)
Ig kappa chain V-I region EU [extracellular region]	Protein	P01598 (Uniprot-TrEMBL)
Ig kappa chain V-I region Gal [extracellular region]	Protein	P01599 (Uniprot-TrEMBL)
Ig kappa chain V-I region HK101 [extracellular region]	Protein	P01601 (Uniprot-TrEMBL)
Ig kappa chain V-I region Hau [extracellular region]	Protein	P01600 (Uniprot-TrEMBL)
Ig kappa chain V-I region Ka [extracellular region]	Protein	P01603 (Uniprot-TrEMBL)
Ig kappa chain V-I region Kue [extracellular region]	Protein	P01604 (Uniprot-TrEMBL)
Ig kappa chain V-I region Lay [extracellular region]	Protein	P01605 (Uniprot-TrEMBL)
Ig kappa chain V-I region Mev [extracellular region]	Protein	P01612 (Uniprot-TrEMBL)
Ig kappa chain V-I region Ni [extracellular region]	Protein	P01613 (Uniprot-TrEMBL)
Ig kappa chain V-I region OU [extracellular region]	Protein	P01606 (Uniprot-TrEMBL)
Ig kappa chain V-I region Rei [extracellular region]	Protein	P01607 (Uniprot-TrEMBL)
Ig kappa chain V-I region Roy [extracellular region]	Protein	P01608 (Uniprot-TrEMBL)
Ig kappa chain V-I region Scw [extracellular region]	Protein	P01609 (Uniprot-TrEMBL)
Ig kappa chain V-I region WAT [extracellular region]	Protein	P80362 (Uniprot-TrEMBL)
Ig kappa chain V-I region WEA [extracellular region]	Protein	P01610 (Uniprot-TrEMBL)
Ig kappa chain V-I region Walker [extracellular region]	Protein	P04431 (Uniprot-TrEMBL)
Ig kappa chain V-I region Wes [extracellular region]	Protein	P01611 (Uniprot-TrEMBL)
Ig kappa chain V-II region Cum [extracellular region]	Protein	P01614 (Uniprot-TrEMBL)
Ig kappa chain V-II region FR [extracellular region]	Protein	P01615 (Uniprot-TrEMBL)
Ig kappa chain V-II region GM607 [extracellular region]	Protein	P06309 (Uniprot-TrEMBL)
Ig kappa chain V-II region MIL [extracellular region]	Protein	P01616 (Uniprot-TrEMBL)
Ig kappa chain V-II region RPMI 6410 [extracellular region]	Protein	P06310 (Uniprot-TrEMBL)
Ig kappa chain V-II region TEW [extracellular region]	Protein	P01617 (Uniprot-TrEMBL)
Ig kappa chain V-III region B6 [extracellular region]	Protein	P01619 (Uniprot-TrEMBL)
Ig kappa chain V-III region CLL [extracellular region]	Protein	P04207 (Uniprot-TrEMBL)
Ig kappa chain V-III region GOL [extracellular region]	Protein	P04206 (Uniprot-TrEMBL)
Ig kappa chain V-III region HAH [extracellular region]	Protein	P18135 (Uniprot-TrEMBL)
Ig kappa chain V-III region HIC [extracellular region]	Protein	P18136 (Uniprot-TrEMBL)
Ig kappa chain V-III region IARC/BL41 [extracellular region]	Protein	P06311 (Uniprot-TrEMBL)
Ig kappa chain V-III region NG9 [extracellular region]	Protein	P01621 (Uniprot-TrEMBL)
Ig kappa chain V-III region POM [extracellular region]	Protein	P01624 (Uniprot-TrEMBL)
Ig kappa chain V-III region SIE [extracellular region]	Protein	P01620 (Uniprot-TrEMBL)
Ig kappa chain V-III region Ti [extracellular region]	Protein	P01622 (Uniprot-TrEMBL)
Ig kappa chain V-III region VG [extracellular region]	Protein	P04433 (Uniprot-TrEMBL)
Ig kappa chain V-III region VH [extracellular region]	Protein	P04434 (Uniprot-TrEMBL)
Ig kappa chain V-III region WOL [extracellular region]	Protein	P01623 (Uniprot-TrEMBL)
Ig kappa chain V-IV region B17 [extracellular region]	Protein	P06314 (Uniprot-TrEMBL)
Ig kappa chain V-IV region JI [extracellular region]	Protein	P06313 (Uniprot-TrEMBL)
Ig kappa chain V-IV region Len [extracellular region]	Protein	P01625 (Uniprot-TrEMBL)
Ig kappa chain V-IV region STH [extracellular region]	Protein	P83593 (Uniprot-TrEMBL)
Ig lambda chain V-III region LOI [extracellular region]	Protein	P80748 (Uniprot-TrEMBL)
Ig lambda chain V-III region SH [extracellular region]	Protein	P01714 (Uniprot-TrEMBL)
Ig lambda chain V-VII region MOT [extracellular region]	Protein	P01720 (Uniprot-TrEMBL)
Ig lambda chain V region 4A [extracellular region]	Protein	P04211 (Uniprot-TrEMBL)
Ig lambda chain V-I region BL2 [extracellular region]	Protein	P06316 (Uniprot-TrEMBL)
Ig lambda chain V-I region EPS [extracellular region]	Protein	P06888 (Uniprot-TrEMBL)
Ig lambda chain V-I region HA [extracellular region]	Protein	P01700 (Uniprot-TrEMBL)
Ig lambda chain V-I region MEM [extracellular region]	Protein	P06887 (Uniprot-TrEMBL)
Ig lambda chain V-I region NEW [extracellular region]	Protein	P01701 (Uniprot-TrEMBL)
Ig lambda chain V-I region NEWM [extracellular region]	Protein	P01703 (Uniprot-TrEMBL)
Ig lambda chain V-I region NIG-64 [extracellular region]	Protein	P01702 (Uniprot-TrEMBL)
Ig lambda chain V-I region VOR [extracellular region]	Protein	P01699 (Uniprot-TrEMBL)
Ig lambda chain V-I region WAH [extracellular region]	Protein	P04208 (Uniprot-TrEMBL)
Ig lambda chain V-II region BO [extracellular region]	Protein	P01710 (Uniprot-TrEMBL)
Ig lambda chain V-II region BOH [extracellular region]	Protein	P01706 (Uniprot-TrEMBL)
Ig lambda chain V-II region BUR [extracellular region]	Protein	P01708 (Uniprot-TrEMBL)
Ig lambda chain V-II region MGC [extracellular region]	Protein	P01709 (Uniprot-TrEMBL)
Ig lambda chain V-II region NEI [extracellular region]	Protein	P01705 (Uniprot-TrEMBL)
Ig lambda chain V-II region NIG-58 [extracellular region]	Protein	P01713 (Uniprot-TrEMBL)
Ig lambda chain V-II region NIG-84 [extracellular region]	Protein	P04209 (Uniprot-TrEMBL)
Ig lambda chain V-II region TOG [extracellular region]	Protein	P01704 (Uniprot-TrEMBL)
Ig lambda chain V-II region TRO [extracellular region]	Protein	P01707 (Uniprot-TrEMBL)
Ig lambda chain V-II region VIL [extracellular region]	Protein	P01711 (Uniprot-TrEMBL)
Ig lambda chain V-II region WIN [extracellular region]	Protein	P01712 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Bau [extracellular region]	Protein	P01715 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Hil [extracellular region]	Protein	P01717 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Kern [extracellular region]	Protein	P01718 (Uniprot-TrEMBL)
Ig lambda chain V-IV region MOL [extracellular region]	Protein	P06889 (Uniprot-TrEMBL)
Ig lambda chain V-IV region X [extracellular region]	Protein	P01716 (Uniprot-TrEMBL)
Ig lambda chain V-V region DEL [extracellular region]	Protein	P01719 (Uniprot-TrEMBL)
Ig lambda chain V-VI region AR [extracellular region]	Protein	P01721 (Uniprot-TrEMBL)
Ig lambda chain V-VI region EB4 [extracellular region]	Protein	P06319 (Uniprot-TrEMBL)
Ig lambda chain V-VI region NIG-48 [extracellular region]	Protein	P01722 (Uniprot-TrEMBL)
Ig lambda chain V-VI region SUT [extracellular region]	Protein	P06317 (Uniprot-TrEMBL)
Ig lambda chain V-VI region WLT [extracellular region]	Protein	P06318 (Uniprot-TrEMBL)
IgH heavy chain V-III region VH26 precursor [extracellular region]	Protein	P01764 (Uniprot-TrEMBL)
IkB(alpha):NF-kB complex	Complex	REACT_12767 (Reactome)
JUN	Protein	P05412 (Uniprot-TrEMBL)
K63polyUb TRAF6 [cytosol]	Protein	Q9Y4K3 (Uniprot-TrEMBL)
K63polyUb-NEMO [cytosol]	Protein	Q9Y6K9 (Uniprot-TrEMBL)
K63polyUb		REACT_21645 (Reactome)
KRAS(1-186) [plasma membrane]	Protein	P01116 (Uniprot-TrEMBL)
LAT-2	Protein	O43561-2 (Uniprot-TrEMBL)
LAT2	Protein	Q9GZY6 (Uniprot-TrEMBL)
LCP2 [cytosol]	Protein	Q13094 (Uniprot-TrEMBL)
LYN(2-512)	Protein	P07948 (Uniprot-TrEMBL)
MALT1 [cytosol]	Protein	Q9UDY8 (Uniprot-TrEMBL)
MALT1	Protein	Q9UDY8 (Uniprot-TrEMBL)
MAP2K4(2-399)	Protein	P45985 (Uniprot-TrEMBL)
MAP2K7	Protein	O14733 (Uniprot-TrEMBL)
MAP3K1(2-1512)	Protein	Q13233 (Uniprot-TrEMBL)
MAP3K7 [cytosol]	Protein	O43318 (Uniprot-TrEMBL)
MAPK8/9/10	Protein	REACT_21895 (Reactome)
MS4A2 [plasma membrane]	Protein	Q01362 (Uniprot-TrEMBL)
MyrG-p-Y420-FYN(2-537) [plasma membrane]	Protein	P06241 (Uniprot-TrEMBL)
NF-kB complex	Complex	REACT_12775 (Reactome)
NF-kB complex	Complex	REACT_12832 (Reactome)
NFAT:CaN:CaM	Complex	REACT_164084 (Reactome)
NFAT:CaN:CaM	Complex	REACT_164266 (Reactome)
NFKB1(1-433) [cytosol]	Protein	P19838 (Uniprot-TrEMBL)
NFKB1(1-433) [nucleoplasm]	Protein	P19838 (Uniprot-TrEMBL)
NFKBIA [cytosol]	Protein	P25963 (Uniprot-TrEMBL)
NRAS [plasma membrane]	Protein	P01111 (Uniprot-TrEMBL)
PAK dimer	Complex	REACT_164900 (Reactome)
PAK1 [cytosol]	Protein	Q13153 (Uniprot-TrEMBL)
PAK2(1-524) [cytosol]	Protein	Q13177 (Uniprot-TrEMBL)
PDK1:PIP2,PIP3	Complex	REACT_12991 (Reactome)
PDPK1 [plasma membrane]	Protein	O15530 (Uniprot-TrEMBL)
PDPK1	Protein	O15530 (Uniprot-TrEMBL)
PI(3,4)P2 [plasma membrane]	Metabolite	CHEBI:16152 (ChEBI)
PI(3,4,5)P3 [plasma membrane]	Metabolite	CHEBI:16618 (ChEBI)
PI(3,4,5)P3	Metabolite	CHEBI:16618 (ChEBI)
PI(4,5)P2	Metabolite	CHEBI:18348 (ChEBI)
PI3K	Complex	REACT_4240 (Reactome)
PIK3CA [cytosol]	Protein	P42336 (Uniprot-TrEMBL)
PIK3CB [cytosol]	Protein	P42338 (Uniprot-TrEMBL)
PIK3R1 [cytosol]	Protein	P27986 (Uniprot-TrEMBL)
PIK3R2 [cytosol]	Protein	O00459 (Uniprot-TrEMBL)
PIP3 activates AKT signaling	Pathway	WP2653 (WikiPathways)	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.
PIP3, PI(3,4)P2	Metabolite	REACT_12804 (Reactome)
PKC-theta (open): DAG	Complex	REACT_13197 (Reactome)
PLC gamma1/2	Protein	REACT_120292 (Reactome)
PLCG1(2-1290) [cytosol]	Protein	P19174 (Uniprot-TrEMBL)
PLCG2 [cytosol]	Protein	P16885 (Uniprot-TrEMBL)
PPP3CA [cytosol]	Protein	Q08209 (Uniprot-TrEMBL)
PPP3CA [nucleoplasm]	Protein	Q08209 (Uniprot-TrEMBL)
PPP3CB(2-524) [cytosol]	Protein	P16298 (Uniprot-TrEMBL)
PPP3CB(2-524) [nucleoplasm]	Protein	P16298 (Uniprot-TrEMBL)
PPP3R1 [cytosol]	Protein	P63098 (Uniprot-TrEMBL)
PPP3R1 [nucleoplasm]	Protein	P63098 (Uniprot-TrEMBL)
PPi	Metabolite	CHEBI:29888 (ChEBI)
PRKCQ [plasma membrane]	Protein	Q04759 (Uniprot-TrEMBL)
PRKQC closed conformation	Protein	Q04759 (Uniprot-TrEMBL)
Phospho-ERK dimer	Complex	REACT_12827 (Reactome)
Phosphorylated NFATC1/2/3	Protein	REACT_120227 (Reactome)
Pi	Metabolite	CHEBI:18367 (ChEBI)
RAC1 [cytosol]	Protein	P63000 (Uniprot-TrEMBL)
RAC1-GDP	Complex	REACT_22018 (Reactome)
RAF/MAP kinase cascade	Pathway	WP2735 (WikiPathways)	The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
RELA [cytosol]	Protein	Q04206 (Uniprot-TrEMBL)
RELA [nucleoplasm]	Protein	Q04206 (Uniprot-TrEMBL)
RasGRPs:DAG:Ca2+	Complex	REACT_164524 (Reactome)
RasGRPs	Protein	REACT_165129 (Reactome)	Rap1 can be activated by certain GEFs that respond to calcium and diacylglycerol (CalDAG-GEFs).
SHC1-2	Protein	P29353-2 (Uniprot-TrEMBL)
SOS1 [cytosol]	Protein	Q07889 (Uniprot-TrEMBL)
SYK [cytosol]	Protein	P43405 (Uniprot-TrEMBL)
SYK/FYN	Complex	REACT_164115 (Reactome)
SYK	Protein	P43405 (Uniprot-TrEMBL)
TAB1 [cytosol]	Protein	Q15750 (Uniprot-TrEMBL)
TAB1:TAB2/TAB3:TAK1	Complex	REACT_21619 (Reactome)
TAB2 [cytosol]	Protein	Q9NYJ8 (Uniprot-TrEMBL)
TAB3(1-712) [cytosol]	Protein	Q8N5C8 (Uniprot-TrEMBL)
TEC,BTK,ITK,(TXK)	Protein	REACT_165246 (Reactome)
TRAF6 [cytosol]	Protein	Q9Y4K3 (Uniprot-TrEMBL)
TRAF6	Protein	Q9Y4K3 (Uniprot-TrEMBL)
UBE2N [cytosol]	Protein	P61088 (Uniprot-TrEMBL)
UBE2V1 [cytosol]	Protein	Q13404 (Uniprot-TrEMBL)
Ub-TRAF6 trimer bound to CBM complex	Complex	REACT_12752 (Reactome)
Ubc13:UBE2V1	Complex	REACT_12995 (Reactome)
VAV1 [cytosol]	Protein	P15498 (Uniprot-TrEMBL)
VAV2 [cytosol]	Protein	P52735 (Uniprot-TrEMBL)
VAV3 [cytosol]	Protein	Q9UKW4 (Uniprot-TrEMBL)
VAV	Protein	REACT_21165 (Reactome)
Zn2+ [cytosol]	Metabolite	CHEBI:29105 (ChEBI)
Zn2+ [nucleoplasm]	Metabolite	CHEBI:29105 (ChEBI)
p-10Y-LAT2 [plasma membrane]	Protein	Q9GZY6 (Uniprot-TrEMBL)
p-10Y-LAT2	Protein	Q9GZY6 (Uniprot-TrEMBL)
p-10Y-NTAL:p-SHC1:GRB2:SOS:GAB2	Complex	REACT_164708 (Reactome)
p-10Y-NTAL:p-SHC1:GRB2:SOS:p-3Y-GAB2:PI3K	Complex	REACT_164935 (Reactome)
p-10Y-NTAL:p-SHC1:GRB2:SOS:p-3Y-GAB2	Complex	REACT_164851 (Reactome)
p-10Y-NTAL:p-SHC1:GRB2:SOS	Complex	REACT_165062 (Reactome)
p-2S-cJUN:p-2S,2T-cFOS	Complex	REACT_21707 (Reactome)
p-2Y-PAK	Protein	REACT_19490 (Reactome)
p-4Y-PLCG1 [plasma membrane]	Protein	P19174 (Uniprot-TrEMBL)
p-4Y-PLCG2 [plasma membrane]	Protein	P16885 (Uniprot-TrEMBL)
p-5Y-LAT-2 [plasma membrane]	Protein	O43561-2 (Uniprot-TrEMBL)
p-5Y-LAT-2	Protein	O43561-2 (Uniprot-TrEMBL)
p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV:RAC1-GTP:PAK dimer	Complex	REACT_164313 (Reactome)
p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV:RAC1-GTP	Complex	REACT_164894 (Reactome)
p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV	Complex	REACT_164523 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:SLP76:PLCG	Complex	REACT_148415 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:SLP76	Complex	REACT_148283 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:TEC kinases:PIP3	Complex	REACT_164096 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-2Y-BTK/p-2Y-ITK:PIP3	Complex	REACT_164249 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-2Y-TEC kinases	Complex	REACT_165277 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-TEC kinases:PIP3	Complex	REACT_164842 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV	Complex	REACT_164209 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG	Complex	REACT_147980 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1	Complex	REACT_148348 (Reactome)
p-5Y-PKC-theta:DAG	Complex	REACT_165187 (Reactome)
p-6Y-SYK [cytosol]	Protein	P43405 (Uniprot-TrEMBL)
p-BCL10 [cytosol]	Protein	O95999 (Uniprot-TrEMBL)
p-MAP2K4/p-MAP2K7	Protein	REACT_21783 (Reactome)
p-MAPK8/9/10		REACT_21549 (Reactome)
p-MAPK8/9/10		REACT_22035 (Reactome)
p-S177,S181-IKBKB [cytosol]	Protein	O14920 (Uniprot-TrEMBL)
p-S177,S181-IKKB:IKKA:NEMO	Complex	REACT_13373 (Reactome)
p-S177,S181-IKKB:IKKA:pUb-NEMO	Complex	REACT_12853 (Reactome)
p-S243-NFATC2 [cytosol]	Protein	Q13469 (Uniprot-TrEMBL)
p-S243-NFATC2 [nucleoplasm]	Protein	Q13469 (Uniprot-TrEMBL)
p-S257,T261-MAP2K4	Protein	P45985 (Uniprot-TrEMBL)
p-S257-NFATC1 [cytosol]	Protein	O95644 (Uniprot-TrEMBL)
p-S257-NFATC1 [nucleoplasm]	Protein	O95644 (Uniprot-TrEMBL)
p-S265-NFATC3 [cytosol]	Protein	Q12968 (Uniprot-TrEMBL)
p-S265-NFATC3 [nucleoplasm]	Protein	Q12968 (Uniprot-TrEMBL)
p-S271,T275-MAP2K7	Protein	O14733 (Uniprot-TrEMBL)
p-S32,S36-NFKBIA	Protein	P25963 (Uniprot-TrEMBL)
p-S552,S645-CARD11(1-1147) [cytosol]	Protein	Q9BXL7 (Uniprot-TrEMBL)
p-S552,S645-CARD11(1-1147)	Protein	Q9BXL7 (Uniprot-TrEMBL)
p-S552-CARD11(1-1147) [cytosol]	Protein	Q9BXL7 (Uniprot-TrEMBL)
p-S63,S73-JUN [nucleoplasm]	Protein	P05412 (Uniprot-TrEMBL)
p-S63,S73-JUN	Protein	P05412 (Uniprot-TrEMBL)
p-SHC1:GRB2:SOS	Complex	REACT_160377 (Reactome)
p-SYK/p-BTK	Complex	REACT_165606 (Reactome)
p-T185,Y187-MAPK1 [nucleoplasm]	Protein	P28482 (Uniprot-TrEMBL)
p-T202,Y204-MAPK3 [nucleoplasm]	Protein	P27361 (Uniprot-TrEMBL)
p-T325,T331,S362,S374-FOS [nucleoplasm]	Protein	P01100 (Uniprot-TrEMBL)
p-T325,T331,S362,S374-FOS	Protein	P01100 (Uniprot-TrEMBL)
p-Y113,Y128,Y145-LCP2 [cytosol]	Protein	Q13094 (Uniprot-TrEMBL)
p-Y1400,Y1412-MAP3K1(2-1512)	Protein	Q13233 (Uniprot-TrEMBL)
p-Y172-VAV2 [cytosol]	Protein	P52735 (Uniprot-TrEMBL)
p-Y173-VAV3 [cytosol]	Protein	Q9UKW4 (Uniprot-TrEMBL)
p-Y174-VAV1 [cytosol]	Protein	P15498 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2 [cytosol]	Protein	P29353-2 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2	Protein	P29353-2 (Uniprot-TrEMBL)
p-Y396-LYN(2-512) [plasma membrane]	Protein	P07948 (Uniprot-TrEMBL)
p-Y396-LYN(2-512)	Protein	P07948 (Uniprot-TrEMBL)
p-Y452,Y476,Y584-GAB2 [cytosol]	Protein	Q9UQC2 (Uniprot-TrEMBL)
p-Y90,T219,T538,S676,S695-PRKCQ [plasma membrane]	Protein	Q04759 (Uniprot-TrEMBL)
p-Y90-PKC-theta:DAG	Complex	REACT_12758 (Reactome)
p-Y90-PRKCQ [plasma membrane]	Protein	Q04759 (Uniprot-TrEMBL)
p21 RAS:GDP	Complex	REACT_2657 (Reactome)
p21 RAS:GTP	Complex	REACT_4782 (Reactome)

Annotated Interactions

View all...

Source	Target	Type	Database reference	Comment
	ADP	Arrow	REACT_12399 (Reactome)
	ADP	Arrow	REACT_163658 (Reactome)
	ADP	Arrow	REACT_163664 (Reactome)
	ADP	Arrow	REACT_163671 (Reactome)
	ADP	Arrow	REACT_163676 (Reactome)
	ADP	Arrow	REACT_163685 (Reactome)
	ADP	Arrow	REACT_163692 (Reactome)
	ADP	Arrow	REACT_163708 (Reactome)
	ADP	Arrow	REACT_163713 (Reactome)
	ADP	Arrow	REACT_163742 (Reactome)
	ADP	Arrow	REACT_163765 (Reactome)
	ADP	Arrow	REACT_163791 (Reactome)
	ADP	Arrow	REACT_163801 (Reactome)
	ADP	Arrow	REACT_163808 (Reactome)
	ADP	Arrow	REACT_163847 (Reactome)
	ADP	Arrow	REACT_163882 (Reactome)
	ADP	Arrow	REACT_163935 (Reactome)
	ADP	Arrow	REACT_163949 (Reactome)
	ADP	Arrow	REACT_163959 (Reactome)
	ADP	Arrow	REACT_163980 (Reactome)
	ADP	Arrow	REACT_163987 (Reactome)
	ADP	Arrow	REACT_163989 (Reactome)
	ADP	Arrow	REACT_163990 (Reactome)
	ADP	Arrow	REACT_21251 (Reactome)
	ADP	Arrow	REACT_6716 (Reactome)
	ADP	Arrow	REACT_6896 (Reactome)
	AMP	Arrow	REACT_163920 (Reactome)
ATP			REACT_12399 (Reactome)
ATP			REACT_163658 (Reactome)
ATP			REACT_163664 (Reactome)
ATP			REACT_163671 (Reactome)
ATP			REACT_163676 (Reactome)
ATP			REACT_163685 (Reactome)
ATP			REACT_163692 (Reactome)
ATP			REACT_163708 (Reactome)
ATP			REACT_163713 (Reactome)
ATP			REACT_163742 (Reactome)
ATP			REACT_163765 (Reactome)
ATP			REACT_163791 (Reactome)
ATP			REACT_163801 (Reactome)
ATP			REACT_163808 (Reactome)
ATP			REACT_163847 (Reactome)
ATP			REACT_163882 (Reactome)
ATP			REACT_163920 (Reactome)
ATP			REACT_163935 (Reactome)
ATP			REACT_163949 (Reactome)
ATP			REACT_163959 (Reactome)
ATP			REACT_163980 (Reactome)
ATP			REACT_163987 (Reactome)
ATP			REACT_163989 (Reactome)
ATP			REACT_163990 (Reactome)
ATP			REACT_21251 (Reactome)
ATP			REACT_6716 (Reactome)
ATP			REACT_6896 (Reactome)
	Active Calmodulin	Arrow	REACT_12602 (Reactome)
Active Calmodulin			REACT_163756 (Reactome)
	Allergin:p-LYN:p-FCERI:IgE aggregate	Arrow	REACT_163959 (Reactome)
Allergin:p-LYN:p-FCERI:IgE aggregate			REACT_163716 (Reactome)
Allergin:p-LYN:p-FCERI:IgE aggregate		mim-catalysis	REACT_163671 (Reactome)
Allergin			REACT_163837 (Reactome)
BCL10:MALT1			REACT_163941 (Reactome)
BCL10			REACT_163827 (Reactome)
CALM1			REACT_12602 (Reactome)
CARD11(1-1147)			REACT_163676 (Reactome)
	Ca2+	Arrow	REACT_12074 (Reactome)
Ca2+			REACT_12074 (Reactome)
Ca2+			REACT_12602 (Reactome)
Ca2+			REACT_163677 (Reactome)
Ca2+			REACT_163756 (Reactome)
Calcineurin (CaN)			REACT_163756 (Reactome)
	Calcineurin:Calmodulin (CaN:CaM)	Arrow	REACT_163756 (Reactome)
Calcineurin:Calmodulin (CaN:CaM)			REACT_163737 (Reactome)
Calcineurin:Calmodulin (CaN:CaM)		mim-catalysis	REACT_163737 (Reactome)
	Clustered p:LYN:p-FCERI:IgE:allergin:SYK	Arrow	REACT_163716 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:SYK			REACT_163708 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:SYK		mim-catalysis	REACT_163708 (Reactome)
	Clustered p:LYN:p-FCERI:IgE:allergin:p-6Y-SYK	Arrow	REACT_163708 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:p-6Y-SYK		mim-catalysis	REACT_163742 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:p-6Y-SYK		mim-catalysis	REACT_163791 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:p-6Y-SYK		mim-catalysis	REACT_163808 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:p-6Y-SYK		mim-catalysis	REACT_163847 (Reactome)
Clustered p:LYN:p-FCERI:IgE:allergin:p-6Y-SYK		mim-catalysis	REACT_163935 (Reactome)
	DAG:p-5Y-PKC-theta:CBM complex	Arrow	REACT_163941 (Reactome)
DAG:p-5Y-PKC-theta:CBM complex			REACT_163827 (Reactome)
	DAG:p-5Y-PKC-theta:CBM oligomer:TRAF6 oligomer	Arrow	REACT_163631 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:TRAF6 oligomer			REACT_163920 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:TRAF6 oligomer		mim-catalysis	REACT_163920 (Reactome)
	DAG:p-5Y-PKC-theta:CBM oligomer:TRAF6	Arrow	REACT_163727 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:TRAF6			REACT_163631 (Reactome)
	DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:TAK1:TAB1:TAB2/3	Arrow	REACT_164005 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:TAK1:TAB1:TAB2/3			REACT_163664 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:TAK1:TAB1:TAB2/3		mim-catalysis	REACT_163664 (Reactome)
	DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:activated TAK1 complex	Arrow	REACT_163664 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6:activated TAK1 complex		mim-catalysis	REACT_163980 (Reactome)
	DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6	Arrow	REACT_163920 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer:oligo-K63-poly Ub-TRAF6			REACT_164005 (Reactome)
	DAG:p-5Y-PKC-theta:CBM oligomer	Arrow	REACT_163827 (Reactome)
DAG:p-5Y-PKC-theta:CBM oligomer			REACT_163727 (Reactome)
	DAG:p-5Y-PKC-theta:p-S552,S645-CARMA1 oligomer	Arrow	REACT_163673 (Reactome)
DAG:p-5Y-PKC-theta:p-S552,S645-CARMA1 oligomer			REACT_163941 (Reactome)
	DAG:p-5Y-PKC-theta:p-S552,S645-CARMA1	Arrow	REACT_163676 (Reactome)
DAG:p-5Y-PKC-theta:p-S552,S645-CARMA1			REACT_163673 (Reactome)
	DAGs	Arrow	REACT_163649 (Reactome)
DAGs			REACT_163677 (Reactome)
DAGs			REACT_163703 (Reactome)
	FCERI:IgE:allergin aggregate	Arrow	REACT_163837 (Reactome)
FCERI:IgE:allergin aggregate			REACT_163959 (Reactome)
FCERI:IgE			REACT_163837 (Reactome)
FOS			REACT_21251 (Reactome)
GAB2			REACT_163700 (Reactome)
GADS:SLP76			REACT_147784 (Reactome)
	GDP	Arrow	REACT_147697 (Reactome)
	GDP	Arrow	REACT_163939 (Reactome)
GRB2:SOS1			REACT_163832 (Reactome)
GTP			REACT_147697 (Reactome)
GTP			REACT_163939 (Reactome)
H2O			REACT_163649 (Reactome)
H2O			REACT_163737 (Reactome)
I(1,4,5)P3		Arrow	REACT_12074 (Reactome)
	I(1,4,5)P3	Arrow	REACT_163649 (Reactome)
I(1,4,5)P3			REACT_12008 (Reactome)
IKKA:IKKB:NEMO			REACT_163980 (Reactome)
IP3 receptor homotetramer			REACT_12008 (Reactome)
	IP3 receptor:IP3 complex	Arrow	REACT_12008 (Reactome)
IP3 receptor:IP3 complex		mim-catalysis	REACT_12074 (Reactome)
IkB(alpha):NF-kB complex			REACT_12399 (Reactome)
JUN			REACT_6716 (Reactome)
K63polyUb			REACT_12553 (Reactome)
K63polyUb			REACT_163920 (Reactome)
LAT-2			REACT_163808 (Reactome)
LAT2			REACT_163935 (Reactome)
LYN(2-512)			REACT_163801 (Reactome)
LYN(2-512)		mim-catalysis	REACT_163801 (Reactome)
MALT1			REACT_163827 (Reactome)
MAP2K4(2-399)			REACT_163987 (Reactome)
MAP2K7			REACT_163949 (Reactome)
MAP3K1(2-1512)			REACT_163685 (Reactome)
MAP3K1(2-1512)		mim-catalysis	REACT_163685 (Reactome)
MAPK8/9/10			REACT_6896 (Reactome)
	NF-kB complex	Arrow	REACT_12399 (Reactome)
	NF-kB complex	Arrow	REACT_163925 (Reactome)
NF-kB complex			REACT_163925 (Reactome)
	NFAT:CaN:CaM	Arrow	REACT_163650 (Reactome)
	NFAT:CaN:CaM	Arrow	REACT_163737 (Reactome)
NFAT:CaN:CaM			REACT_163650 (Reactome)
PAK dimer			REACT_163979 (Reactome)
	PDK1:PIP2,PIP3	Arrow	REACT_12641 (Reactome)
PDPK1			REACT_12641 (Reactome)
	PI(3,4,5)P3	Arrow	REACT_163990 (Reactome)
PI(3,4,5)P3			REACT_163692 (Reactome)
PI(3,4,5)P3			REACT_163700 (Reactome)
PI(3,4,5)P3			REACT_163881 (Reactome)
PI(4,5)P2			REACT_163649 (Reactome)
PI(4,5)P2			REACT_163990 (Reactome)
PI3K			REACT_163929 (Reactome)
PIP3, PI(3,4)P2			REACT_12641 (Reactome)
	PKC-theta (open): DAG	Arrow	REACT_163703 (Reactome)
PKC-theta (open): DAG			REACT_163671 (Reactome)
PLC gamma1/2			REACT_147817 (Reactome)
	PPi	Arrow	REACT_163920 (Reactome)
PRKQC closed conformation			REACT_163703 (Reactome)
Phospho-ERK dimer		mim-catalysis	REACT_21251 (Reactome)
Phosphorylated NFATC1/2/3			REACT_163737 (Reactome)
	Pi	Arrow	REACT_163737 (Reactome)
RAC1-GDP			REACT_163939 (Reactome)
			REACT_12008 (Reactome)	The IP3 receptor (IP3R) is an IP3-gated calcium channel. It is a large, homotetrameric protein, similar to other calcium channel proteins such as ryanodine. The four subunits form a 'four-leafed clover' structure arranged around the central calcium channel. Binding of ligands such as IP3 results in conformational changes in the receptor's structure that leads to channel opening.
			REACT_12074 (Reactome)	IP3 promotes the release of intracellular calcium.
			REACT_12399 (Reactome)	NF-kB is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins, called IkBs, which mask the nuclear localization signal (NLS) of NF-kB and prevent its nuclear translocation. A key event in NF-kB activation involves phosphorylation of IkB (at sites equivalent to Ser32 and Ser36 of IkB-alpha or Ser19 and Ser22 of IkB-beta) by IKK. The phosphorylated IkB-alpha is recognized by the E3 ligase complex and targeted for ubiquitin-mediated proteasomal degradation, releasing the NF-kB dimer p50/p65 into the nucleus to turn on target genes. (Karin & Ben-Neriah 2000)
			REACT_12553 (Reactome)	During the phosphorylation of the IKK beta, the regulatory subunit NEMO undergoes K-63-linked polyubiquitination. Ubiquitinated TRAF6 trimer, acts as a E3 ligase and induces this ubiquitination. The ubiquitin target sites in NEMO are not yet clearly identified. Studies of different NF-kB signaling pathways revealed several potential ubiquitination sites on NEMO (e.g., K285, K277, K309 and K399) (Fuminori et al. 2009).
			REACT_12602 (Reactome)	Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions.
			REACT_12641 (Reactome)	PI3K activation results in recruitment of the serine/threonine kinase PDK1, (3-phosphoinositide-dependent kinase 1) to the plasma membrane where PDK1 subsequently phosphorylates and activates AKT. PDK1 with its PH domain binds to either PIP3 or PIP2 and is translocated to the plasma membrane. PDK1 seems to exist in an active, phosphorylated configuration under basal conditions (Vanhaesebroeck & Alessi 2000).
			REACT_147697 (Reactome)	GRB2-bound SOS promotes the formation of active GTP-bound RAS. This activates the mitogen-activated protein kinase (MAPK) cascade, leading to cell growth and differentiation.
			REACT_147717 (Reactome)	GRB2 is an adapter protein that contains a central SH2 domain flanked by N- and C-terminal SH3 domains. GRB2 acts downstream of receptor protein-tyrosine kinases and is involved in Ras and MAP kinase pathway activation by associating with the guanine exchange factor (GEF) SOS. GRB2 is constitutively bound to SOS through its SH3 domains, which interact with a proline-rich sequence in the C-terminal part of SOS (Chardin et al. 1993). Following phosphorylation of LAT, the GRB2:SOS complex binds to the phosphorylated tyrosines and is thereby translocated to the inner face of the plasma membrane where inactive RAS:GDP resides. The three distal tyrosines, Y171, Y191 and Y226 of LAT are responsible for GRB2 association (Balagopalan et al. 2010, Zhang et al. 2000).
			REACT_147784 (Reactome)	Gads/GRAP2 (GRB2-related adapter protein 2) is member of the GRB2 adaptor family with a central SH2 domain and linker region flanked by amino- and carboxy-terminal SH3 domains. SLP-76 associates constitutively via its central 20-amino acid proline-rich domain with the C-terminal SH3 domain of Gads, which recruits it to LAT following receptor stimulation. Upon LAT phosphorylation, Gads:SLP-76 complex principally binds to phosphorylated LAT tyrosine 191, with a reduced amount of binding to phosphorylated tyrosine 171 and no interaction with phosphorylated tyrosines 132 or 226 (Houtman et al. 2004, Zhu et al. 2003). Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways (Liu et al. 1999). The LAT-Gads-SLP-76 complex creates a platform for the recruitment of multiple signaling molecules, including PLCgamma1, GRB2, NCK, Rho GEFs, VAV and the Tec-family kinases ITK and BTK (Liu et al. 1999 & 2001, Asada et al. 1999, Yablonski et al. 2001).
			REACT_147817 (Reactome)	The phospholipase PLC-gamma is an important mediator of TCR, FCERI and DAP12 signal transduction. PLC-gamma hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) and in-turn promotes the Ca+2 influx and activation of NFAT. Activation of PLC-gamma1 entails the binding of PLC-gamma1 to both LAT and SLP-76 adapter proteins. The amino-terminal SH2 domain of PLC-gamma1 was shown to preferentially bind phosphorylated LAT Y132 with high affinity and no detectable binding to phosphorylated tyrosines 171, 191, and 226. PLC-gamma1 was also shown to bind the adapter protein SLP-76 indirectly through GADS, which is bound to LAT at Y171 and Y191. SH3 domain of PLC-gamma1 associates with the proline-rich region of SLP-76 (Yablonski et al. 2001). PLC-gamma1 associates with Gads/SLP-76 complex before binding to p-Y132 of LAT (Houtman et al. 2005). PLC-gamma1 association with LAT is stabilized by Gads/SLP-76 bound to LAT (Zhu et al.2003). Association of PLC-gamma to LAT and SLP-76 couples it to the kinases (Syk and Tec family kinase) required for tyrosine phosphorylation and activation of PLC-gamma. Mast cells express both PLC-gamma1 and PLC-gamma2 isoforms, which are phosphorylated by BTK/ITK and/or SYK. FCERI-dependent Ca2+ release requires the recruitment of PLC-gamma by SLP-76 and LAT. In mast cells, increased intracellular calcium triggers rapid release of preformed mediators, through a process of vesicle exocytosis, known as degranulation. Recruitment and activation of phospholipase C gamma (PLC-gamma) is involved in DAP12 signal transduction. Phosphorylation of multiple substrates including PLC-gamma1 has been observed in Ly49D/DAP12 triggered NK cells (McVicar et al. 1998). In myeloid cells, PLC-gamma2 is recruited and then phosphorylated upon activation of TREM2 and DAP12 (Peng et al. 2010).
			REACT_163631 (Reactome)	BCL10-MALT1 oligomers bind to TRAF6 and this inturn promotes the oligomerization of TRAF6 and activates its E3 ligase activity (Sun et al. 2004).
			REACT_163649 (Reactome)	Phosphoinositol 4,5-bisphosphate (PIP2) is cleaved in to two most important second messengers diacylglycerol (DAG) and Inositol 1,4,5-triphosphate (IP3) by phospholipase C (PLC). DAG remains within the membrane and activates protein kinase C (PKC) while IP3 leaves the cell membrane and binds to IP3 receptor that releases Ca2+ from endoplasmic reticulum (ER).
			REACT_163650 (Reactome)	Dephosphorylated NFAT-calcineurin (CaN) complex translocates to nucleus, where it activates transcription of several cytokine genes (e.g..IL2).
			REACT_163658 (Reactome)	Upon dimer disassociation PAK1 autophosphorylates in both cis- and trans- manner. Serine 144 (S144) in the GTPase-binding domain and threonine 423 (T423) in the activation loop are the target sites for autophosphorylation (Parrini et al. 2002).
			REACT_163664 (Reactome)	Binding of TAB2 and TAB3 to K63-linked polyubiquitin chains leads to the activation of TAK1 by an uncertain mechanism. Phosphorylation of TAK1 within the activation loop of the kinase is absolutely required for TAK1 activity. TAB1 is known to augment TAK1 catalytic activity by mediating spontaneous oligomerization and induces autophosphorylation of TAK1 (Kishimoto et al. 2000). The binding of TAB2/3 to polyubiquitinated TRAF6 may facilitate polyubiquitination of TAB2/3 by TRAF6 (Ishitani et al. 2003), which might result in conformational changes within the TAK1 complex that leads to the activation of TAK1. Some biochemical studies revealed that free K63 polyubiquitin chains, which are not conjugated to any cellular protein, can directly activate the TAK1 kinase complex (Xia et al. 2009).
			REACT_163671 (Reactome)	Raft localized PKC-theta is phosphorylated and is activated. Phosphorylation of both tyrosine and serine-threonine residues is important in the regulation of PKC function. Six phosphorylation sites have been identified on PKC-theta: Y90, T219, T538, S676, S685, and S695. Phosphorylation of Y90 positively regulates NF-AT and NF-kB activation in T-cells. In mast cells Src family members Src and LYN have been shown to be involved in phosphorylating Y90 (Wang et al. 2012, Liu et al. 2001).
			REACT_163673 (Reactome)	CARMA1 phosphorylation initiates its oligomerization and the coiled-coil (CC) domain of CARMA1 is hypothesized to mediate this clustering (Tanner et al. 2007).
			REACT_163676 (Reactome)	CARMA1 (CARD11/Caspase recruitment domain-containing protein 11), BCL10 (B-cell lymphoma/leukemia 10) and MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1)/paracaspase have been identified as signaling components that act downstream of PKC-theta. CARMA1 is a scaffold protein and recruits BCL10, MALT1, PKC and TRAF6 to form a multi protein complex. CARMA1 exists in an inactive conformation in which the linker region binds to and blocks the accessibility of the CARD motif. Upon stimulation S552 and S645 linker residues are phosphorylated by PKC-theta and this may weaken this interaction, inducing an open conformation of CARMA1. Further phosphorylation studies have revealed other phosphorylation sites (S109, S551 and S555) that may also promote activation of CARMA1. Serene/threonine kinases PKC-beta, IKKbeta, HPK1 and CaMKII are involved in triggering CARMA1 activation (Thome et al. 2010, Rueda & Thome 2005). (only phosphorylated S552 and S645 are represented in this reaction)
			REACT_163677 (Reactome)	Ras guanyl nucleotide-releasing proteins (RasGRPs) are guanyl nucleotide exchange factors (GEFs) that activate Ras ultimately leading to MAPK activation. RasGRPs have a catalytic domain composed of Ras exchange motif (REM) and a CDC25 domain, an atypical pair of EF hands that bind calcium and a DAG-binding C1 domain. After PIP2 hydrolysis, RasGRPs are recruited to the plasma membrane by binding to DAG and calcium (Stone 2011, Liu et al. 2007). Upon T-cell activation RasGRP1 specifically interacts with and activates Ras on Golgi instead of the plasma membrane (Bivona et al. 2003). It remains to be determined whether activation of N-Ras by RasGRP1 in mast cells occurs in the Golgi or the plasma membrane (Liu et al. 2007). RasGRP4 is mast cell specific and is involved in the controls Ras activation.
			REACT_163685 (Reactome)	FCERI aggregation has been shown to activate JNK as well as protein kinases upstream of JNK, such as MEKK1 (Mitogen-activated protein kinase/ERK Kinase Kinase-1) and JNK kinase (JNKK). PAK has been shown to be the upstream kinase involved in the activation of MEKK1, however no direct phosphorylation of MEKK1 by PAK is observed. Two threonine residues at positions 1400 and 1412 (analogous to 1381 and 1393 in mouse) in the activation loop of MEKK1 between the kinase subdomains VII and VIII are essential for its catalytic activity. The catalytic domain of MEKK1 is able to autophosphorylate these residues, enhancing its own activity.
			REACT_163692 (Reactome)	Phosphorylation of VAV stimulates its GEF activity for RAC1, and thus it plays an important role in linking FCERI to the RAC1-JNK pathway. VAV exists in an auto-inhibitory state, folded in such a way as to inhibit the GEF activity of its DH domain. This folding is mediated through binding of tyrosines in the acidic domain to the DH domain and through binding of the calponin homology (CH) domain to the C1 region. Activation of VAV may involve three events which relieve this auto-inhibition: phosphorylation of tyrosines in the acidic domain causes them to be displaced from the DH domain; binding of a ligand to the CH domain may cause it to release the C1 domain; binding of the PI3K product PIP3 to the PH domain may alter its conformation (Aghazadeh et al. 2000). VAV is phosphorylated on tyrosine residue (Y174 in VAV1/172 in VAV2/173 in VAV3) in the acidic domain. This is mediated by SYK and Src-family tyrosine kinases (Deckert et al. 1996, Schuebel et al. 1998). Once activated, VAV is involved in the activation of RAC1, PAK1, MEK and ERK and cytokine production.
			REACT_163700 (Reactome)	NTAL cooperates with LAT in mast cells to activate PI3K pathway and cytokine production through Grb2-associated binding protein 2 (GAB2) (Gonzalez-Espinosa et al. 2003). FCERI aggregation induced translocation of a significant fraction of GAB2 from the cytosol to the plasma membrane by binding GRB2. Two of the proline-rich motifs in GAB2 are binding sites for the SH3 of GRB2. GAB2 is also recruited to plasma membrane by binding to phosphatidylinositol-3,4,5-trisphosphate (PIP3) with its plecstrin homology (PH) domain. GAB2 can be recruited to FCERI indirectly through GRB2 bound SHC1. SHC1 is recruited to the FCERI beta chain through its SH2 domain and becomes tyrosyl-phosphorylated. Phosphorylated SHC provides a docking site for the GRB2 and this in turn recruits GAB2 (Yu et al. 2006). GAB2 and PI3K are required for FCERI-induced granule translocation.
			REACT_163703 (Reactome)	DAG along with intracellular calcium signals cooperatively to activate PKCs, which then trigger other pathways such as the NF-kB pathway, ultimately leading to mast cell degranulation and cytokine production (Wu 2011). MCs express several Protein kinase C (PKC) isozymes and these kinases are involved in both the activation and termination of the degranulation process. PKC-delta is a negative regulator of FCERI mediated mast cell degranulation, whereas PKC-theta facilitates in degranulation (Leitges et al. 2002, Liu et al. 2001). In response to FCERI activation PKC-theta translocates to membrane by binding to DAG with its C1 domain. PKC-theta exists in two conformations closed/inactive and open/active state. In resting state, PKC-theta is autoinhibited where the pseudosubstrate sequence in the N-terminal regulatory region of PKC-theta forms intramolecular interaction with the substrate-binding region in the catalytic domain. This prevents the catalytic domain gaining access to substrates. The allosteric change of PKC-theta from closed to open state involves two important mechanisms: DAG binding to the C1 domains and autophosphorylation of T538 on the activation loop. Interaction with DAG induces conformational change resulting in the exposure of the activation loop of PKC-theta (Wang et al. 2012, Melowic et al. 2007).
			REACT_163708 (Reactome)	Multiple sites of phosphorylation are known to exist in SYK, which both regulate its activity and also serve as docking sites for other proteins. Some of these sites include Y131 of interdomain A, Y323, Y348, and Y352 of interdomain B, and Y525 and Y526 within the activation loop of the kinase domain and Y630 in the C-terminus (Zhang et al. 2002, Lupher et al. 1998, Furlong et al. 1997). Phosphorylation of these tyrosine residues disrupts autoinhibitory interactions and results in kinase activation even in the absence of phosphorylated ITAM tyrosines (Tsang et al. 2008). SYK is primarily phosphorylated by Src family kinases and this acts as an initiating trigger by generating few molecules of activated SYK which are then involved in major SYK autophosphorylation (Hillal et al. 1997).
			REACT_163712 (Reactome)	VAV an activator of RAC-GTPases, is redistributed to plasma membrane and is phosphorylated following engagement of FCERI. Phosphorylated SLP-76 tyrosines Y113 and Y128 (112Y and 128Y in mouse) provide binding sites for the SH2 domains of VAV. The binding of VAV to these phosphotyrosine residues may link SLP-76 to the Jun amino-terminal kinase (JNK) pathway and the actin cytoskeleton (Kettner et al. 2003). In addition to its known role as guanine nucleotide exchange factor (GEF), VAV also modulates cytokine production in mast cells. VAV1-deficient bone marrow-derived mast cells exhibited reduced degranulation and cytokine production and calcium release in addition of reduced activation of c-Jun NH2-terminal kinase 1 (JNK1), although tyrosine phosphorylation of FCERI, SYK and LAT was normal (Manetz et al. 2001, Arudchandran et al. 2000, Song et al. 1999).
			REACT_163713 (Reactome)	T219, T538 at the activation loop, S676 at the turn motif and S695 at the hydrophobic motif are autophosphorylated in cis-maanner. Posphorylation of T538 is critical for kinase activation and it stabilises the open active conformation. Some studies suggest the involvement of PDK1 (3-phosphoinositide-dependent protein kinase 1) and GLK kinases in the phosphorylation T538.
			REACT_163716 (Reactome)	Tyrosine phosphorylated ITAM in FCERI gamma subunit serves as docking site for SYK (spleen tyrosine kinases), whereas the beta-subunit ITAM has an extra tyrosine and is shorter than canonical ITAM which makes it unfit to bind SYK. Association of SYK to FCERI gamma-subunit disrupts the COOH-terminal-SH2 interdomain interaction of SYK causing a conformational change opening the molecule leading to its activation (Siraganian et al. 2010, de Castro et al. 2010).
			REACT_163727 (Reactome)	TRAF6 is a ubiquitin ligase that plays a central role in the IKK-dependent canonical NF-kB pathway. It is recruited to the CBM complex by binding to MALT1. The MALT1 C-terminal Ig domain and extension contain two binding motifs for TRAF6 (Noels et al 2007). After oligomerzation TRAF6, together with Ubc13/Uev1A, activates TAK1 and IKK. It also acts as an E3 ligase for MALT1 and mediates lysine 63-linked ubiquitination (Oeckinghaus et al. 2007).
			REACT_163737 (Reactome)	Nuclear factor of activated T-cells (NFAT) is a transcription factor which induces genes responsible for cytokine production, for cell-cell interactions etc. NFAT transcription activity is modulated by calcium and Calcineurin concentration. In resting cells NFAT is phosphorylated and resides in the cytoplasm. Phosphorylation sites are located in NFAT's regulatory domain in three different serine rich motifs, termed SRR1, SP2 and SP. Upon stimulation, these serine residues are dephosphorylated by calcineurin, that thought to cause exposure of nuclear localization signal sequences triggering translocation of the dephosphorylated NFAT-CaN complex to the nucleus. Among all the phosphorylation sites one of the site in SRR-2 motif is not susceptable to dephosphorylation by CaN (Takeuchi et al. 2007, Hogan et al. 2003).
			REACT_163742 (Reactome)	SLP-76 lacks intrinsic catalytic activity and acts as a scaffold, recruiting other proteins for correct localization during molecular signal transduction (Bogin et al. 2007). Activation of FCERI leads to tyrosine phosphorylation of SLP-76 (Gross et al. 1999). SLP-76 has three potential tyrosine phosphorylation sites within its amino terminus region: Y113, Y128, and Y145. Phosphorylation may be mediated by SYK, analogous to the role of ZAP-70 in phosphorylating T-cell SLP-76 (Bubeck-Wardenberg et al. 1996).
			REACT_163756 (Reactome)	Calcineurin (CaN), also called protein phosphatase 2B (PP2B), is a calcium/Calmodulin (CaM)-dependent serine/threonine protein phosphatase. It exists as a heterodimer consisting of CaM-binding catalytic subunit CaN A chain and a Ca+2 binding regulatory CaN B chain. At low calcium concentrations, CaN exists in an inactive state, where the autoinhibitory domain (AID) binds to the active-site cleft. Upon an increase in calcium concentration CaM binds to Ca+2 ions and gets activated. Active CaM binds to CaN regulatory domain (RD) and this causes release of the AID and activation of the phosphatase (Rumi-Masante et al. 2012). Binding of calcium to CaN B regulatory chain also causes a conformational change of the RD of CaN A chain (Yang & Klee 2000).
			REACT_163765 (Reactome)	Tyrosine phosphorylation of PLC-gamma enhances its catalytic activity. BTK and SYK are involved in the phosphorylation of PLC-gamma (PLCG). Phosphorylation of tyrosine residues 753, 759, 1197, and 1217 in PLCG2 and 771, 783, and 1254 in PLCG1 have been identified as BTK/SYK-dependent phosphorylation sites.
			REACT_163791 (Reactome)	SHC is an adapter protein that has been implicated in Ras activation. Mast cells express two isoforms of 46 and 52 kDa. Both isoforms of SHC have two domains, an N-terminal phosphotyrosine-binding (PTB) domain and a C-terminal SH2 domain that allows Shc to bind to proteins containing phosphorylated tyrosine residues. Following receptor stimulation, SHC is phosphorylated by Src kinases Syk on Y239, Y240 and Y317 (p56 isoform). Both phosphotyrosines Y239 and Y317 creates the binding site for the SH2 domain of GRB2.
			REACT_163801 (Reactome)	LYN localized in lipid rafts undergoes an intermolecular autophosphorylation at tyrosine 396. This residue is present in the activation loop, and its phosphorylation promotes LYN kinase activity.
			REACT_163808 (Reactome)	LAT is palmitoylated and membrane-associated adaptor protein. It rapidly becomes tyrosine-phosphorylated upon receptor engagement. LAT has nine conserved tyrosine residues of which five have been shown to undergo phosphorylation (Y127, Y132, Y171, Y191 and Y226). Src family kinases, SYK and ZAP-70 efficiently phosphorylate LAT on these tyrosine residues (Jiang & Cheng 2007, Paz et al. 2001). Phosphorylation of LAT creates binding sites for the Src homology 2 (SH2) domain proteins PLC-gamma1, GRB2 and GADS, which indirectly bind SOS, VAV, SLP-76 and ITK (Wange 2000).
			REACT_163827 (Reactome)	BCL10 and MALT1 proteins form high molecular weight oligomers and only these oligomeric forms can activate IKK in vitro (Sun et al. 2004). BCL10 proteins form homo-oligomers through CARD-CARD interactions whereas in MALT1 the tandem Ig-like domains naturally form oligomers with a tendency towards dimers and tetramers (Dong et al. 2006, Quiu & Dhe-Paganon 2011). These CBM oligomers provides the molecular platform, which can facilitate dimerization or serve as scaffolds on which proteases and kinases involved in NF-kB activation are assembled and activated.
			REACT_163832 (Reactome)	GRB2 is an adapter protein that contains a central SH2 domain flanked by N- and C-terminal SH3 domains. GRB2 acts downstream of receptor protein-tyrosine kinases and is involved in Ras and MAP kinase pathway activation by associating with the guanine exchange factor (GEF) SOS. GRB2 is constitutively bound to SOS through its SH3 domains, which interact with a proline-rich sequence in the C-terminal part of SOS (Chardin et al. 1993). GRB2-SOS complex binds to phosphotyrosine Y239 and Y317 of SHC1. SHC1 associates with the tyrosine-phosphorylated ITAMs of the FCERI beta-chain and can recruit SOS to membrane. SHC1 and SOS have also been described to associate with LAT via GRB2. Shc binding to Phospho-ITAMs (in vitro binding to phospho peptides) has never been linked to any biological function (activation) and is probably not relevant in a physiological setting.
			REACT_163837 (Reactome)	FCERI is primarily expressed on mast cells and basophils as a tetrameric complex comprising an IgE-binding alpha subunit, a signal amplifying membrane-tetraspanning beta subunit, and a disulfide-linked gamma chain dimer that provides the receptor its signaling competence (Blank & Rivera 2004). In the absence of an antigen or allergen, FCERI receptor binds to monomeric IgE antibodies, and thus the receptor adopts the antigenic specificity of the prevalent IgE repertoire (Garman et al. 2000). Mast cell activation is initiated when multivalent antigen crosslinks the IgE bound to the high-affinity FCERI, thereby aggregating FCERI (Siraganian 2003). Antigen driven aggregation of FCERI then elicits intracellular signals that result in mast cell exocytosis.
			REACT_163841 (Reactome)	Upon phosphorylation NATL/LAT2 recruits GRB2:SOS complex into the receptor-signaling complex. Residues Y95, Y118, Y136, Y193, Y233 are the putative GRB2-binding sites on NTAL (Iwaki et al. 2007).
			REACT_163847 (Reactome)	BTK/ITK are activated in a two step model. In the first step they are recruited to the membrane by binding to PIP3 or, alternatively with other binding partners like SLP-76. Once at the membrane SYK or Src-kinases in the vicinity phosphorylates Y551 (Y512 in ITK) in the activation loop of the catalytic domain of BTK to fully activate it (Rawlings et al. 1996, Park et al. 1996, Kawakami et al. 1994).
			REACT_163881 (Reactome)	Mast cells express four out of five Tec family members (i.e. BTK, ITK, RLK and TEC) and are activated upon cross-linking of FCERI. They are recruited to the membrane via the interaction of their PH domain with PtdIns(3,4,5)P3 phosphate and their SH2 domain with Y145 of SLP-76 (Kettner et al. 2003). BTK is more important for early response such as phosphorylation of PLC-gamma2 and Ca2+ mobilization, whereas ITK regulates the late responses such as changes in gene expression and cytokine secretion. BTK deficient mice have mild defects in degranulation and severe impairments in the production of proinflammatory cytokines upon FCERI cross-linking (Hata et al. 1998). ITK deficient mice have been reported to have reduced MC degranulation and responses to allergic asthma (Forssell et al. 2005). However, Bone marrow derived mast cells (BMMC) derived from ITK deficient mice display a normal degranulation response but secrete elevated level of cytokines (TNFa and IL-13) (Iyer & August 2008). TEC kinase is also one of the crucial regulators of murine mast cell function. TEC is phosphorylated and activated upon FCERI stimulation. TEC deficient bone marrow derived mast cells did not show any in vitro or in vivo defects in histamine release. However, the generation of the leukotriene LTC4 was severely impaired in the absence of TEC (Schmidt et al. 2009).
			REACT_163882 (Reactome)	GAB2 have multiple tyrosyl phosphorylation sites that are phosphorylated up on activation of FCERI. SYK is the major tyrosine kinase involved in GAB2 phosphorylation. FYN is also shown to contribute to GAB2 tyrosyl phosphorylation but it is not clear whether GAB2 is a direct substrate of FYN (Yu et al. 2006, Parravicini et al. 2002). GAB2 tyrosines (Y452, Y476 and Y584) in the YXXM motif can be the target phosphorylation sites for SYK/FYN kinases (Chan et al. 2010, Harir et al. 2007).
			REACT_163920 (Reactome)	TRAF6 possesses ubiquitin ligase activity and undergoes K-63-linked auto-ubiquitination after its oligomerization. In the first step, ubiquitin is activated by an E1 ubiquitin activating enzyme. The activated ubiquitin is transferred to a E2 conjugating enzyme (a heterodimer of proteins Ubc13 and Uev1A) forming the E2-Ub thioester. Finally, in the presence of ubiquitin-protein ligase E3 (TRAF6, a RING-domain E3), ubiquitin is attached to the target protein (TRAF6 on residue Lysine 124) through an isopeptide bond between the C-terminus of ubiquitin and the epsilon-amino group of a lysine residue in the target protein. In contrast to K-48-linked ubiquitination that leads to the proteosomal degradation of the target protein, K-63-linked polyubiquitin chains act as a scaffold to assemble protein kinase complexes and mediate their activation through proteosome-independent mechanisms. This K63 polyubiquitinated TRAF6 activates the TAK1 kinase complex.
			REACT_163925 (Reactome)	The released NF-kB transcription factor (p50/p65) with unmasked nuclear localization signal (NLS) then moves in to the nucleus. Once in the nucleus, NF-kB binds DNA and regulate the expression of genes encoding cytokines, cytokine receptors, and apoptotic regulators.
			REACT_163929 (Reactome)	Phosphorylated Y452, Y476, and Y584 of GAB2 binds p85 regulatory subunit of PI3K kinase, resulting in activation of PI3K pathway. PI3K is required for mast cell degranulation and anaphylaxis response but not for cytokine production or contact hypersensitivity (Nishida et al. 2011). Activated PI3K generates second messenger PtdInsP3 (PIP3) at the inner membrane, which provides docking sites for pleckstrin homology (PH) domains of PDK1, AKT and BTK. Activated AKT controls major downstream targets like mTORC1, FOXO3 and GSK3beta pathways that regulate mast cell growth, homeostasis, and cytokine production. BTK triggers PLCgamma2 activation, thereby inducing activation of the transcription factor NFAT and NF-kB.
			REACT_163935 (Reactome)	NTAL and LAT play complementary roles in the positive regulation of FCERI-mediated degranulation. Upon FCERI aggregation NTAL is phosphorylated by LYN, SYK and KIT on different tyrosines. Phosphorylated NTAL likely contributes to the activation of mast cells by providing docking sites for the recruitment of critical signaling molecules into the lipid raft. There are about ten tyrosines in LAT2 of which five tyrosines principally phosphorylated by SYK are recognised as putative GRB2-binding sites, being part of a YXN motif, whereas LYN and KIT phosphorylate both tyrosines contained in the YXN motifs as well as tyrosines outside of the YXN motifs (Iwaki et al. 2008).
			REACT_163939 (Reactome)	Rac1 exists in inactive state in the cytosol until the reception of extracellular signals by the cell. To be functional Rac1 is rapidly targeted to the plasma membrane upon cell stimulation. The main factors involved in this mobilisation are the Rac GEFs like VAV and phospholipids (PtdIns(4,5)P2, PtdIns(3,4,5) P3) and lipid rafts at the plasma membrane. VAV catalyses the disassociation of GDP from Rac1 by modifying the nucleotide-binding site such that GDP is released and subsequently replaced. The incoming GTP occupies the nucleotide binding site and finally displaces VAV from Rac1 (Bos et al. 2007, Bustelo et al. 2012).
			REACT_163941 (Reactome)	Phosphorylation of CARMA1 causes conformational change such that its CARD motif is exposed and is free to interact with BCL10 CARD motif. BCL10 constitutively associated with MALT1 and exists as a preformed complex in the cytoplasm. BCL10 and MALT1 have been identified as key positive regulators of FCERI-dependent NF-kB activation (Klemm et al. 2006). The resulting CARMA1-BCL10-MALT1 (CBM) complex may be stabilized by interactions between the CARMA1 coiled coil (CC) domain and a C-terminal MALT1 region that lacks the DD and first two Ig domains (Thome et al. 2010, Che et al. 2004). The CBM complex transmits activating signals that ultimately result in ubiquitination (Ub) and degradation of the NF-kB inhibitor, IkBa.
			REACT_163949 (Reactome)	MKK7 is activated by MEKK1 and the residues serine 271 and threonine 275 are the potential phosphorylation sites that are crucial for its kinase activity (phosphorylation sites are based on sequence alignment with MAP kinase kinase family members).
			REACT_163959 (Reactome)	Upon FCGRI-IgE aggregation, LYN kinase phosphorylates the tyrosine residues within the ITAM (immunoreceptor tyrosine-based activation motifs) of both the beta and gamma subunits. The detailed mechanism of the initial engagement of LYN kinase and FCERI is incompletely understood, but two different models have been proposed. One model postulates that a small fraction of LYN is constitutively bound to beta subunit of FCERI prior to activation. Aggregation of FCERI facilitates the transphosphorylation of one FCERI by LYN bound to a juxtaposed receptor (Vonakis et al. 1997, Draber & Draberova 2002). Alternative model postulates that LYN is observed in lipid rafts enriched in glycosphingolipids, cholesterol, and glycosylphosphatidylinositol-anchored proteins and upon aggregation, FCERI rapidly translocates into lipid rafts, where it is phosphorylated by LYN kinase. Either the association of LYN or FCERI or both with lipid rafts is important for initiating this phosphorylation process (Young et al. 2003, Kovarova et al. 2002, Draber & Draberova 2002). Beta subunit ITAM differs from canonical ITAMs in two ways; the spacing between the two canonical tyrosines harbours a third tyrosine, and it is one amino acid shorter than in canonical ITAMs, thus making it unfit to bind and recruit Syk. Among the three tyrosine residues (Y219, Y225 and Y229), Y219 may play a predominant role in beta chain function and LYN recruitment. Mutation of this tyrosine would decrease substantially LYN association and subsequent phosphorylation of Y225 and Y229. This would result in decreased gamma phosphorylation and decreased SYK recruitment and activation (On et al. 2004).
			REACT_163979 (Reactome)	PAK1 kinase is a member of serine/threonine protein kinase family and is widely believed as mediator between Cdc42 and Rac1 and the JNK signal transduction pathway. PAK1 is involved in regulating FCERI mediated mast cell degranulation via effects on calcium mobilisation and cytoskeletal changes (Allen et al. 2009). The conventional PAK family contains a N-terminal conserved Cdc42/Rac-interacting binding domain (CRIB) that overlaps a kinase inhibitory (KI) domain and a C-terminal catalytic domain. PAK1 molecules form trans-inhibited homodimers in which the N-terminal kinase inhibitory (KI) domain of one PAK1 molecule in the dimer binds and inhibits the C-terminal catalytic domain of the other. Isoprenylated Rac1/Cdc42-GTP localized to the membrane recruits PAK1 by binding to the N-terminal CRIB domain. Binding of activated Cdc42/Rac1, breaks the PAK1-dimer and removes the trans-inhibition and stimulates serine/threonine kinase activity of that allows autophosphorylation (Lu & Mayer 1999, Parrini et all. 2009, Zhao et al. 2005).
			REACT_163980 (Reactome)	In humans, the IkB kinase (IKK) complex serves as the master regulator for the activation of NF-kB by various stimuli. It contains two catalytic subunits, IKK alpha and IKK beta, and a regulatory subunit, IKKgamma/NEMO. The activation of IKK complex is dependent on the phosphorylation of IKK alpha/beta at its activation loop and the K63-linked ubiquitination of NEMO. This basic trimolecular complex is referred to as the IKK complex. IKK subunits have a N-term kinase domain a leucine zipper (LZ) motifs, a helix-loop-helix (HLH) and a C-ter NEMO binding domain (NBD). IKK catalytic subunits are dimerized through their LZ motifs. IKK beta is the major IKK catalytic subunit for NF-kB activation. Activated TAK1 phosphorylate IKK beta on S177 and S181 (S176 and S180 in IKK alpha) in the activation loop and thus activate the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation.
			REACT_163987 (Reactome)	Activated MEKK1 then phosphorylates and activates SAPK/Erk kinase (SEK1), also known as MKK4 or Jun kinase kinase (JNKK) on serine and threonine residues at positions 257 and 261, respectively.
			REACT_163989 (Reactome)	After initial phosphorylation by SFK's, subsequently Y223 (Y180 in ITK and Y206 in TEC) in the SH3 domain of BTK is autophosphorylated, which may prevent inhibitory intramolecular interactions (Nore et al. 2003, Joseph et al. 2007, Park et al. 1996)
			REACT_163990 (Reactome)	PI3K catalyzes the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3). This PIP3 acts as a membrane anchor for the downstream proteins like PDK1 and AKT.
			REACT_164005 (Reactome)	K-63 linked polyubiquitin (pUb) chain on TRAF6 provides a scaffold to recruit downstream effector molecules to activate NF-kB. Transforming growth factor beta-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase (MAPK) kinase kinase family is shown to be an essential intermediate that transmits the upstream signals from the receptor complex to the downstream MAPKs and to the NF-kB pathway (Broglie et al. 2009). TAK1-binding protein 1 (TAB1), TAB2 and TAB3 constitutively bound to TAK1. TAB1 acts as the activation subunit of the TAK1 complex, aiding in the autophosphorylation of TAK1, whereas TAB2 and its homologue TAB3, act as a adaptors of TAK1 that facilitate the assembly of TAK1 complex to TRAF6. The highly conserved C-terminal zinc finger domain of TAB2 and TAB3 binds preferentially to the K-63-linked polyubiquitin chains on TRAF6 (Broglie et al. 2009, Besse et al. 2007).
			REACT_21251 (Reactome)	The Fos proteins(c-Fos, FosB, Fra1 and Fra2), which cannot homodimerize, form stable heterodimers with Jun proteins and thereby enhance their DNA binding activity. On activation of the MAPK pathway, Ser-374 of Fos is phosphorylated by ERK1/2 and Ser-362 is phosphorylated by RSK1/2, the latter kinases being activated by ERK1/2. If stimulation of the MAPK pathway is sufficiently sustained, ERK1/2 can dock on an upstream FTYP amino acid motif, called the DEF domain (docking site for ERKs, FXFP), and phosphorylate Thr-331 and Thr-325. Phosphorylation at specific sites enhances the transactivating potential of several AP-1 proteins, including Jun and Fos, without having any effect on their DNA binding activities. Thus, phosphorylation of Ser-362 and Ser-374 stabilizes c-Fos but has no demonstrated role in the control of transcriptional activity. On the contrary, phosphorylation of Thr-325 and Thr-331 enhances c-Fos transcriptional activity but has no demonstrated effect on protein turnover.
			REACT_21385 (Reactome)	c-Jun NH2 terminal kinase (JNK) plays a role in conveying signals from the cytosol to the nucleus, where they associate and activate their target transcription factors.
			REACT_21404 (Reactome)	The bZIP domains of Jun and Fos form an X-shaped -helical structure, which binds to the palindromic AP-1 site (TGAGTCA) (Glover and Harrison, 1995).
			REACT_6716 (Reactome)	JNK (c-Jun N-terminal Kinase) phosphorylates several transcription factors including c-Jun after translocation to the nucleus.
			REACT_6896 (Reactome)	Activated human JNK kinases (MKK4 and MKK7) phosphorylate Thr183 and Tyr185 residues in the characteristic Thr-Pro-Tyr phosphoacceptor loop of each JNK. JNK is differentially regulated by MKK4 and MKK7 depending on the stimulus. MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 cascade requires both MKK4 and MKK7. Some studies reported that in three JNK isoforms tested MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine residue (Thr-183).
	RasGRPs:DAG:Ca2+	Arrow	REACT_163677 (Reactome)
RasGRPs			REACT_163677 (Reactome)
SHC1-2			REACT_163791 (Reactome)
SYK/FYN		mim-catalysis	REACT_163882 (Reactome)
SYK			REACT_163716 (Reactome)
TAB1:TAB2/TAB3:TAK1			REACT_164005 (Reactome)
TEC,BTK,ITK,(TXK)			REACT_163881 (Reactome)
TRAF6			REACT_163631 (Reactome)
TRAF6			REACT_163727 (Reactome)
Ub-TRAF6 trimer bound to CBM complex		mim-catalysis	REACT_12553 (Reactome)
	Ubc13:UBE2V1	Arrow	REACT_12553 (Reactome)
	Ubc13:UBE2V1	Arrow	REACT_163920 (Reactome)
Ubc13:UBE2V1			REACT_12553 (Reactome)
Ubc13:UBE2V1			REACT_163920 (Reactome)
VAV			REACT_163712 (Reactome)
	p-10Y-LAT2	Arrow	REACT_163935 (Reactome)
p-10Y-LAT2			REACT_163841 (Reactome)
	p-10Y-NTAL:p-SHC1:GRB2:SOS:GAB2	Arrow	REACT_163700 (Reactome)
p-10Y-NTAL:p-SHC1:GRB2:SOS:GAB2			REACT_163882 (Reactome)
	p-10Y-NTAL:p-SHC1:GRB2:SOS:p-3Y-GAB2:PI3K	Arrow	REACT_163929 (Reactome)
p-10Y-NTAL:p-SHC1:GRB2:SOS:p-3Y-GAB2:PI3K		mim-catalysis	REACT_163990 (Reactome)
	p-10Y-NTAL:p-SHC1:GRB2:SOS:p-3Y-GAB2	Arrow	REACT_163882 (Reactome)
p-10Y-NTAL:p-SHC1:GRB2:SOS:p-3Y-GAB2			REACT_163929 (Reactome)
	p-10Y-NTAL:p-SHC1:GRB2:SOS	Arrow	REACT_163841 (Reactome)
p-10Y-NTAL:p-SHC1:GRB2:SOS			REACT_163700 (Reactome)
	p-2S-cJUN:p-2S,2T-cFOS	Arrow	REACT_21404 (Reactome)
	p-2Y-PAK	Arrow	REACT_163658 (Reactome)
p-2Y-PAK		Arrow	REACT_163685 (Reactome)
	p-5Y-LAT-2	Arrow	REACT_163808 (Reactome)
p-5Y-LAT-2			REACT_147717 (Reactome)
	p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV:RAC1-GTP:PAK dimer	Arrow	REACT_163979 (Reactome)
p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV:RAC1-GTP:PAK dimer			REACT_163658 (Reactome)
p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV:RAC1-GTP:PAK dimer		mim-catalysis	REACT_163658 (Reactome)
	p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV:RAC1-GTP	Arrow	REACT_163658 (Reactome)
	p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV:RAC1-GTP	Arrow	REACT_163939 (Reactome)
p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV:RAC1-GTP			REACT_163979 (Reactome)
	p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV	Arrow	REACT_163692 (Reactome)
p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV			REACT_163939 (Reactome)
p-5Y-LAT:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:PIP3:p-VAV		mim-catalysis	REACT_163939 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:SLP76:PLCG	Arrow	REACT_147817 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:SLP76:PLCG			REACT_163742 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:SLP76	Arrow	REACT_147784 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:SLP76			REACT_147817 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:TEC kinases:PIP3	Arrow	REACT_163881 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:TEC kinases:PIP3			REACT_163847 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-2Y-BTK/p-2Y-ITK:PIP3	Arrow	REACT_163765 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-2Y-BTK/p-2Y-ITK:PIP3		mim-catalysis	REACT_163649 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-2Y-TEC kinases	Arrow	REACT_163989 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-2Y-TEC kinases			REACT_163765 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-TEC kinases:PIP3	Arrow	REACT_163847 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-TEC kinases:PIP3			REACT_163989 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV:p-TEC kinases:PIP3		mim-catalysis	REACT_163989 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV	Arrow	REACT_163712 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV			REACT_163692 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG1:VAV			REACT_163881 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG	Arrow	REACT_163742 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1:GADS:p-Y113,Y128,Y145-SLP-76:PLCG			REACT_163712 (Reactome)
	p-5Y-LAT:p-SHC1:GRB2:SOS1	Arrow	REACT_147717 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1			REACT_147784 (Reactome)
p-5Y-LAT:p-SHC1:GRB2:SOS1		mim-catalysis	REACT_147697 (Reactome)
	p-5Y-PKC-theta:DAG	Arrow	REACT_163713 (Reactome)
p-5Y-PKC-theta:DAG			REACT_163676 (Reactome)
p-5Y-PKC-theta:DAG		mim-catalysis	REACT_163676 (Reactome)
p-MAP2K4/p-MAP2K7		mim-catalysis	REACT_6896 (Reactome)
	p-MAPK8/9/10	Arrow	REACT_21385 (Reactome)
	p-MAPK8/9/10	Arrow	REACT_6896 (Reactome)
p-MAPK8/9/10			REACT_21385 (Reactome)
p-MAPK8/9/10		mim-catalysis	REACT_6716 (Reactome)
	p-S177,S181-IKKB:IKKA:NEMO	Arrow	REACT_163980 (Reactome)
p-S177,S181-IKKB:IKKA:NEMO			REACT_12553 (Reactome)
	p-S177,S181-IKKB:IKKA:pUb-NEMO	Arrow	REACT_12553 (Reactome)
p-S177,S181-IKKB:IKKA:pUb-NEMO		mim-catalysis	REACT_12399 (Reactome)
	p-S257,T261-MAP2K4	Arrow	REACT_163987 (Reactome)
	p-S271,T275-MAP2K7	Arrow	REACT_163949 (Reactome)
	p-S32,S36-NFKBIA	Arrow	REACT_12399 (Reactome)
p-S552,S645-CARD11(1-1147)			REACT_163673 (Reactome)
	p-S63,S73-JUN	Arrow	REACT_6716 (Reactome)
p-S63,S73-JUN			REACT_21404 (Reactome)
	p-SHC1:GRB2:SOS	Arrow	REACT_163832 (Reactome)
p-SHC1:GRB2:SOS			REACT_147717 (Reactome)
p-SHC1:GRB2:SOS			REACT_163841 (Reactome)
p-SYK/p-BTK		mim-catalysis	REACT_163765 (Reactome)
	p-T325,T331,S362,S374-FOS	Arrow	REACT_21251 (Reactome)
p-T325,T331,S362,S374-FOS			REACT_21404 (Reactome)
	p-Y1400,Y1412-MAP3K1(2-1512)	Arrow	REACT_163685 (Reactome)
p-Y1400,Y1412-MAP3K1(2-1512)		mim-catalysis	REACT_163949 (Reactome)
p-Y1400,Y1412-MAP3K1(2-1512)		mim-catalysis	REACT_163987 (Reactome)
	p-Y239,Y240,Y317-SHC1-2	Arrow	REACT_163791 (Reactome)
p-Y239,Y240,Y317-SHC1-2			REACT_163832 (Reactome)
	p-Y396-LYN(2-512)	Arrow	REACT_163801 (Reactome)
p-Y396-LYN(2-512)			REACT_163959 (Reactome)
p-Y396-LYN(2-512)		mim-catalysis	REACT_163959 (Reactome)
	p-Y90-PKC-theta:DAG	Arrow	REACT_163671 (Reactome)
p-Y90-PKC-theta:DAG			REACT_163713 (Reactome)
p21 RAS:GDP			REACT_147697 (Reactome)
	p21 RAS:GTP	Arrow	REACT_147697 (Reactome)