Signaling by type 1 insulin-like growth factor 1 receptor (IGF1R) (Homo sapiens)

From WikiPathways

Revision as of 13:48, 8 May 2014 by Anwesha (Talk | contribs)
Jump to: navigation, search
2, 4, 11, 14, 28...17, 45373721, 22, 26, 49, 50379, 30425316, 18, 31, 36, 40...7, 348, 24, 43, 6132, 58276, 15, 19, 21, 25...101, 10543, 5, 7, 23, 29...373, 7, 33, 38, 39, 46...7, 9, 2210106010p21 RAS phospho-IRSPI3K PI3K-regulatory subunit p-IRS1/2/4 p21 RASGTP PIP3Phosphorylated PKB complex cytosolautophosphorylated IGF1R GRB2SOS1 IGF1/2p-IGF1R IGF1/2 IGF1/2 IGF1/2 TSC1TSC2 eIF4E4E-BP1-P IGF1/2 RhebGTP IGF1/2p-IGF1Rp-IRS1/2/4 IGF1/2 IGF1R GRB2SOSIRS-P p-SHC1 IGF1/2p-IGF1R phospho-IRS IGF1/2p-IGF1R IGF1/2p-IGF1RIRS1/4 IGF1/2p-IGF1RIRS1/2/4 IGF1/2 IGF1R autophosphorylated IGF1R p21 RAS IRS1/4 IGF1/2 SHC1 PI3K RhebGTP PI3K autophosphorylated IGF1R p21 RASGDP PIP3PDK1 complex autophosphorylated IGF1R eIF4E4E-BP IRS1/2/4 TSC1Inhibited TSC2-1-P PI3K-catalytic subunit IGF1/2p-IGF1R RhebGDP Activated mTORC1 IGF1/2 IGF1/2p-IGF1R PIP3AKT2 complex GRB2SOS1 p-IRS1,2 PI3K-catalytic subunit IGF1/2p-IGF1R PKBPKB Regulator PI3K-regulatory subunit GRB2SOS1 autophosphorylated IGF1R IGF1/2p-IGF1RIRS2 autophosphorylated IGF1R GRB2SOSPhospho-SHC autophosphorylated IGF1R IGF1/2IGF1R p-SHC IGF1/2p-IGF1RSHC1 PKB regulator IGF1/2p-IGF1R IGF1/2p-IGF1Rp-SHC1 PIK3CA MTOR PIP3PDK1 complexIGF1RAKT2 p-Y349,Y350,Y427-SHC1 IGF1 EIF4G1PI3KRHEB Energy dependent regulation of mTOR by LKB1-AMPKEIF4EBP1 RPS6KB1ATPADPp-Y-SHC1 ATPp-Y-SHC3 ATPGTPIGF1/2p-IGF1Rp-IRS1/2/4p21 RASGDPMLST8IRS2GDP ADPADPTSC1 p-SHCp-IRS1,2GTP IRS4 ATPSHC1-2 IGF2AKT2 p-S422-EIF4BPIK3CA MTORp-6Y-IRS1 KRASEIF4Bp-Y-IRS4 GRB2SOSPhospho-SHCATPKRASp-S722,S792-RPTOR-1ADPp-T37,T46-EIF4EBP1 ATPp-S371,T389-RPS6KB1GRB2SOS1ATPADPIGF1RADPIGF1RIRS1/4p-S366-EEF2KIGF1RIGF1/2p-IGF1RIRS1/4IRS2 p-Y1161,Y1165,Y1166-IGF1Rp-S939,S1130,T1462-TSC2 IGF1 p-Y1161,Y1165,Y1166-IGF1RTSC2PIP3 3',5'-Cyclic AMPp21 RASGTPH2Op-S1108,S1148,S1192-EIF4G1GTPp-Y-IRS2 PIADPPIP3Phosphorylated PKB complexADPADPPIP3 GRB2-1 IGF1Rp-Y1161,Y1165,Y1166-IGF1RIGF2TRIB3 p-Y-IRS2 GRB2SOSIRS-PGDPp-Y1161,Y1165,Y1166-IGF1RTHEM4 ADPPKBPKB RegulatorTSC1 IGF1/2p-IGF1RIGF2p-Y-IRS2 ATPHRASEIF4Ep-Y239,Y240,Y317-SHC1-2 RhebGDPPDE3BGDPPIK3R2 IGF2NRAS IGF1 IRS2 IGF1/2p-IGF1Rp-SHC1GDP TSC1Inhibited TSC2-1-PAMPEIF4E p-Y1161,Y1165,Y1166-IGF1RRhebGTPPIP3 ADPATPHRASIGF1 p-Y1161,Y1165,Y1166-IGF1RPIK3CB EEF2KIGF1 SHC1NRAS p-S318-PDE3Bp-Y-IRS1 eIF4E4E-BP1-PPIK3R1 PIK3CB ATPphospho-IRSIGF1Rphospho-IRSPI3KPDPK1 p-Y-SHC2 PDPK1IGF2ATPIRS4 p-T37,T46-EIF4EBP1ADPRPTORSHC1-1PIP3IRS1 p-Y1161,Y1165,Y1166-IGF1RGRB2-1 IGF2ATPIRS1 ATPIGF1 p-S939,S1130,T1462-TSC2IGF1RIGF1 p-Y-IRS1 ADPIGF1/2p-IGF1RSHC1IGF1RGRB2-1 AKT2 IGF1RTSC1TSC2ADPActivated mTORC1eIF4E4E-BPGTP RHEB IGF1/2IGF1RIGF1/2PIP3AKT2 complexPIP3IGF1RIGF1RIGF1/2p-IGF1RIRS1/2/4RHEB GTP RPS6IGF1Rp-5S-RPS6RAF/MAP kinase cascadep-Y194,Y195,Y272-SHC1-1IGF1 RPTOR p-Y-DOK1 IGF1/2p-IGF1RIRS2SOS1 SHC1 PIK3R1 TSC2 ATPSOS1 SOS1 PIK3R2 Activated PI3KIGF2EIF4E PKB regulatorMLST8 IGF24020, 48404012, 62, 636133, 557, 401313


Description

Binding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS-RAS-RAF-MAPK (ERK) pathway and the PI3K-PKB (AKT) pathway (recently reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et al. 2010, Parella et al. 2010, Annunziata et al. 2011, Siddle et al. 2012, Holzenberger 2012). Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2404192

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Amoui M, Craddock BP, Miller WT.; ''Differential phosphorylation of IRS-1 by insulin and insulin-like growth factor I receptors in Chinese hamster ovary cells.''; PubMed Europe PMC Scholia
  2. Annunziata M, Granata R, Ghigo E.; ''The IGF system.''; PubMed Europe PMC Scholia
  3. Germain-Lee EL, Janicot M, Lammers R, Ullrich A, Casella SJ.; ''Expression of a type I insulin-like growth factor receptor with low affinity for insulin-like growth factor II.''; PubMed Europe PMC Scholia
  4. Steele-Perkins G, Turner J, Edman JC, Hari J, Pierce SB, Stover C, Rutter WJ, Roth RA.; ''Expression and characterization of a functional human insulin-like growth factor I receptor.''; PubMed Europe PMC Scholia
  5. LeBon TR, Jacobs S, Cuatrecasas P, Kathuria S, Fujita-Yamaguchi Y.; ''Purification of insulin-like growth factor I receptor from human placental membranes.''; PubMed Europe PMC Scholia
  6. Cuevas EP, Escribano O, Chiloeches A, Ramirez Rubio S, Román ID, Fernández-Moreno MD, Guijarro LG.; ''Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2 proliferation.''; PubMed Europe PMC Scholia
  7. Maki RG.; ''Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer.''; PubMed Europe PMC Scholia
  8. Keyhanfar M, Booker GW, Whittaker J, Wallace JC, Forbes BE.; ''Precise mapping of an IGF-I-binding site on the IGF-1R.''; PubMed Europe PMC Scholia
  9. Alvino CL, McNeil KA, Ong SC, Delaine C, Booker GW, Wallace JC, Whittaker J, Forbes BE.; ''A novel approach to identify two distinct receptor binding surfaces of insulin-like growth factor II.''; PubMed Europe PMC Scholia
  10. Maly P, Lüthi C.; ''Characterization of affinity-purified type I insulin-like growth factor receptor from human placenta.''; PubMed Europe PMC Scholia
  11. Rakatzi I, Stosik M, Gromke T, Siddle K, Eckel J.; ''Differential phosphorylation of IRS-1 and IRS-2 by insulin and IGF-I receptors.''; PubMed Europe PMC Scholia
  12. Karas M, Koval AP, Zick Y, LeRoith D.; ''The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II.''; PubMed Europe PMC Scholia
  13. Downward J.; ''PI 3-kinase, Akt and cell survival.''; PubMed Europe PMC Scholia
  14. Stenkula KG, Thorn H, Franck N, Hallin E, Sauma L, Nystrom FH, Strålfors P.; ''Human, but not rat, IRS1 targets to the plasma membrane in both human and rat adipocytes.''; PubMed Europe PMC Scholia
  15. Turjanski AG, Vaqué JP, Gutkind JS.; ''MAP kinases and the control of nuclear events.''; PubMed Europe PMC Scholia
  16. 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
  17. Kyriakis JM, Avruch J.; ''Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.''; PubMed Europe PMC Scholia
  18. 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
  19. Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J.; ''The structural basis of the activation of Ras by Sos.''; PubMed Europe PMC Scholia
  20. Parrella E, Longo VD.; ''Insulin/IGF-I and related signaling pathways regulate aging in nondividing cells: from yeast to the mammalian brain.''; PubMed Europe PMC Scholia
  21. Holzenberger M.; ''Igf-I signaling and effects on longevity.''; PubMed Europe PMC Scholia
  22. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
  23. Roskoski R.; ''ERK1/2 MAP kinases: structure, function, and regulation.''; PubMed Europe PMC Scholia
  24. Giorgetti S, Pelicci PG, Pelicci G, Van Obberghen E.; ''Involvement of Src-homology/collagen (SHC) proteins in signaling through the insulin receptor and the insulin-like-growth-factor-I-receptor.''; PubMed Europe PMC Scholia
  25. Okada S, Pessin JE.; ''Interactions between Src homology (SH) 2/SH3 adapter proteins and the guanylnucleotide exchange factor SOS are differentially regulated by insulin and epidermal growth factor.''; PubMed Europe PMC Scholia
  26. Plotnikov A, Zehorai E, Procaccia S, Seger R.; ''The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.''; PubMed Europe PMC Scholia
  27. Casella SJ, Han VK, D'Ercole AJ, Svoboda ME, Van Wyk JJ.; ''Insulin-like growth factor II binding to the type I somatomedin receptor. Evidence for two high affinity binding sites.''; PubMed Europe PMC Scholia
  28. Brown MD, Sacks DB.; ''Protein scaffolds in MAP kinase signalling.''; PubMed Europe PMC Scholia
  29. Xu B, Bird VG, Miller WT.; ''Substrate specificities of the insulin and insulin-like growth factor 1 receptor tyrosine kinase catalytic domains.''; PubMed Europe PMC Scholia
  30. Tartare-Deckert S, Sawka-Verhelle D, Murdaca J, Van Obberghen E.; ''Evidence for a differential interaction of SHC and the insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system.''; PubMed Europe PMC Scholia
  31. Kim B, Leventhal PS, White MF, Feldman EL.; ''Differential regulation of insulin receptor substrate-2 and mitogen-activated protein kinase tyrosine phosphorylation by phosphatidylinositol 3-kinase inhibitors in SH-SY5Y human neuroblastoma cells.''; PubMed Europe PMC Scholia
  32. Ward CW, Gough KH, Rashke M, Wan SS, Tribbick G, Wang J.; ''Systematic mapping of potential binding sites for Shc and Grb2 SH2 domains on insulin receptor substrate-1 and the receptors for insulin, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor.''; PubMed Europe PMC Scholia
  33. Skolnik EY, Batzer A, Li N, Lee CH, Lowenstein E, Mohammadi M, Margolis B, Schlessinger J.; ''The function of GRB2 in linking the insulin receptor to Ras signaling pathways.''; PubMed Europe PMC Scholia
  34. Karlsson M, Thorn H, Danielsson A, Stenkula KG, Ost A, Gustavsson J, Nystrom FH, Strålfors P.; ''Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes. Cholesterol depletion blocks insulin signalling for metabolic and mitogenic control.''; PubMed Europe PMC Scholia
  35. Fantin VR, Sparling JD, Slot JW, Keller SR, Lienhard GE, Lavan BE.; ''Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells.''; PubMed Europe PMC Scholia
  36. Zoncu R, Efeyan A, Sabatini DM.; ''mTOR: from growth signal integration to cancer, diabetes and ageing.''; PubMed Europe PMC Scholia
  37. Cascieri MA, Chicchi GG, Applebaum J, Hayes NS, Green BG, Bayne ML.; ''Mutants of human insulin-like growth factor I with reduced affinity for the type 1 insulin-like growth factor receptor.''; PubMed Europe PMC Scholia
  38. Cseh B, Doma E, Baccarini M.; ''"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.''; PubMed Europe PMC Scholia
  39. McKay MM, Morrison DK.; ''Integrating signals from RTKs to ERK/MAPK.''; PubMed Europe PMC Scholia
  40. Craparo A, O'Neill TJ, Gustafson TA.; ''Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor.''; PubMed Europe PMC Scholia
  41. Roberts PJ, Der CJ.; ''Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.''; PubMed Europe PMC Scholia
  42. 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
  43. Schreyer S, Ledwig D, Rakatzi I, Klöting I, Eckel J.; ''Insulin receptor substrate-4 is expressed in muscle tissue without acting as a substrate for the insulin receptor.''; PubMed Europe PMC Scholia
  44. Pavelić J, Matijević T, Knezević J.; ''Biological & physiological aspects of action of insulin-like growth factor peptide family.''; PubMed Europe PMC Scholia
  45. Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
  46. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
  47. Yu KT, Peters MA, Czech MP.; ''Similar control mechanisms regulate the insulin and type I insulin-like growth factor receptor kinases. Affinity-purified insulin-like growth factor I receptor kinase is activated by tyrosine phosphorylation of its beta subunit.''; PubMed Europe PMC Scholia
  48. He W, O'Neill TJ, Gustafson TA.; ''Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains.''; PubMed Europe PMC Scholia
  49. Hernández-Sánchez C, Blakesley V, Kalebic T, Helman L, LeRoith D.; ''The role of the tyrosine kinase domain of the insulin-like growth factor-I receptor in intracellular signaling, cellular proliferation, and tumorigenesis.''; PubMed Europe PMC Scholia
  50. Ravichandran LV, Esposito DL, Chen J, Quon MJ.; ''Protein kinase C-zeta phosphorylates insulin receptor substrate-1 and impairs its ability to activate phosphatidylinositol 3-kinase in response to insulin.''; PubMed Europe PMC Scholia
  51. Takahashi Y, Tobe K, Kadowaki H, Katsumata D, Fukushima Y, Yazaki Y, Akanuma Y, Kadowaki T.; ''Roles of insulin receptor substrate-1 and Shc on insulin-like growth factor I receptor signaling in early passages of cultured human fibroblasts.''; PubMed Europe PMC Scholia
  52. Siddle K.; ''Molecular basis of signaling specificity of insulin and IGF receptors: neglected corners and recent advances.''; PubMed Europe PMC Scholia
  53. Alvino CL, Ong SC, McNeil KA, Delaine C, Booker GW, Wallace JC, Forbes BE.; ''Understanding the mechanism of insulin and insulin-like growth factor (IGF) receptor activation by IGF-II.''; PubMed Europe PMC Scholia
  54. Cargnello M, Roux PP.; ''Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.''; PubMed Europe PMC Scholia
  55. Bürgisser DM, Roth BV, Giger R, Lüthi C, Weigl S, Zarn J, Humbel RE.; ''Mutants of human insulin-like growth factor II with altered affinities for the type 1 and type 2 insulin-like growth factor receptor.''; PubMed Europe PMC Scholia
  56. He W, Craparo A, Zhu Y, O'Neill TJ, Wang LM, Pierce JH, Gustafson TA.; ''Interaction of insulin receptor substrate-2 (IRS-2) with the insulin and insulin-like growth factor I receptors. Evidence for two distinct phosphotyrosine-dependent interaction domains within IRS-2.''; PubMed Europe PMC Scholia
  57. Huang M, Lai WP, Wong MS, Yang M.; ''Effect of receptor phosphorylation on the binding between IRS-1 and IGF-1R as revealed by surface plasmon resonance biosensor.''; PubMed Europe PMC Scholia
  58. Kim B, van Golen CM, Feldman EL.; ''Insulin-like growth factor-I signaling in human neuroblastoma cells.''; PubMed Europe PMC Scholia
  59. Wellbrock C, Karasarides M, Marais R.; ''The RAF proteins take centre stage.''; PubMed Europe PMC Scholia
  60. Chitnis MM, Yuen JS, Protheroe AS, Pollak M, Macaulay VM.; ''The type 1 insulin-like growth factor receptor pathway.''; PubMed Europe PMC Scholia
  61. Duronio V.; ''Insulin receptor is phosphorylated in response to treatment of HepG2 cells with insulin-like growth factor I.''; PubMed Europe PMC Scholia
  62. Kim B, Cheng HL, Margolis B, Feldman EL.; ''Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling.''; PubMed Europe PMC Scholia
  63. Qu BH, Karas M, Koval A, LeRoith D.; ''Insulin receptor substrate-4 enhances insulin-like growth factor-I-induced cell proliferation.''; PubMed Europe PMC Scholia
  64. Siemeister G, al-Hasani H, Klein HW, Kellner S, Streicher R, Krone W, Müller-Wieland D.; ''Recombinant human insulin receptor substrate-1 protein. Tyrosine phosphorylation and in vitro binding of insulin receptor kinase.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
129733view01:45, 22 May 2024EweitzModified title
114848view16:35, 25 January 2021ReactomeTeamReactome version 75
113294view11:36, 2 November 2020ReactomeTeamReactome version 74
112506view15:46, 9 October 2020ReactomeTeamReactome version 73
101418view11:30, 1 November 2018ReactomeTeamreactome version 66
100956view21:06, 31 October 2018ReactomeTeamreactome version 65
100493view19:41, 31 October 2018ReactomeTeamreactome version 64
100038view16:24, 31 October 2018ReactomeTeamreactome version 63
99591view14:58, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99210view12:43, 31 October 2018ReactomeTeamreactome version 62
93994view13:50, 16 August 2017ReactomeTeamreactome version 61
93603view11:28, 9 August 2017ReactomeTeamreactome version 61
87189view08:08, 19 July 2016EgonwOntology Term : 'signaling pathway' added !
86709view09:24, 11 July 2016ReactomeTeamreactome version 56
83075view09:53, 18 November 2015ReactomeTeamVersion54
81398view12:55, 21 August 2015ReactomeTeamVersion53
76867view08:14, 17 July 2014ReactomeTeamFixed remaining interactions
76572view11:55, 16 July 2014ReactomeTeamFixed remaining interactions
75905view09:56, 11 June 2014ReactomeTeamRe-fixing comment source
75605view10:45, 10 June 2014ReactomeTeamReactome 48 Update
74960view13:48, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74604view08:39, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
3',5'-Cyclic AMPMetaboliteCHEBI:17489 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
AKT2 ProteinP31751 (Uniprot-TrEMBL)
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated PI3KComplexREACT_9165 (Reactome)
Activated mTORC1ComplexREACT_7770 (Reactome)
EEF2KProteinO00418 (Uniprot-TrEMBL)
EIF4BProteinP23588 (Uniprot-TrEMBL)
EIF4E ProteinP06730 (Uniprot-TrEMBL)
EIF4EBP1 ProteinQ13541 (Uniprot-TrEMBL)
EIF4EProteinP06730 (Uniprot-TrEMBL)
EIF4G1ProteinQ04637 (Uniprot-TrEMBL)
Energy dependent regulation of mTOR by LKB1-AMPKPathwayREACT_21387 (Reactome) Upon formation of a trimeric LKB1:STRAD:MO25 complex, LKB1 phosphorylates and activates AMPK. If the AMP:ATP ratio rises, this activation is maintained and AMPK activates the TSC complex by phosphorylating TSC2. Active TSC activates the intrinsic GTPase activity of Rheb, resulting in GDP-loaded Rheb and inhibition of mTOR pathway.
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRB2

SOS

IRS-P		ComplexREACT_3414 (Reactome)
GRB2

SOS

Phospho-SHC		ComplexREACT_2380 (Reactome)
GRB2 SOS1ComplexREACT_4435 (Reactome)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HRASProteinP01112 (Uniprot-TrEMBL)
IGF1 ProteinP05019 (Uniprot-TrEMBL)
IGF1/2 IGF1RComplexREACT_151821 (Reactome)
IGF1/2

p-IGF1R

IRS1/2/4		ComplexREACT_150878 (Reactome)
IGF1/2

p-IGF1R

IRS1/4		ComplexREACT_151270 (Reactome)
IGF1/2

p-IGF1R

IRS2		ComplexREACT_151257 (Reactome)
IGF1/2

p-IGF1R

SHC1		ComplexREACT_151215 (Reactome)
IGF1/2

p-IGF1R

p-IRS1/2/4		ComplexREACT_151884 (Reactome)
IGF1/2

p-IGF1R

p-SHC1		ComplexREACT_151817 (Reactome)
IGF1/2 p-IGF1RComplexREACT_150608 (Reactome)
IGF1/2ProteinREACT_17556 (Reactome)
IGF1RProteinP08069 (Uniprot-TrEMBL)
IGF1RComplexREACT_152174 (Reactome)
IGF2ProteinP01344 (Uniprot-TrEMBL)
IRS1 ProteinP35568 (Uniprot-TrEMBL)
IRS1/4ProteinREACT_150840 (Reactome)
IRS2 ProteinQ9Y4H2 (Uniprot-TrEMBL)
IRS2ProteinQ9Y4H2 (Uniprot-TrEMBL)
IRS4 ProteinO14654 (Uniprot-TrEMBL)
KRASProteinP01116 (Uniprot-TrEMBL)
MLST8 ProteinQ9BVC4 (Uniprot-TrEMBL)
MLST8ProteinQ9BVC4 (Uniprot-TrEMBL)
MTOR ProteinP42345 (Uniprot-TrEMBL)
MTORProteinP42345 (Uniprot-TrEMBL)
NRAS ProteinP01111 (Uniprot-TrEMBL)
PDE3BProteinQ13370 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
PDPK1 ProteinO15530 (Uniprot-TrEMBL)
PDPK1ProteinO15530 (Uniprot-TrEMBL)
PI3KComplexREACT_4240 (Reactome)
PIMetaboliteCHEBI:18348 (ChEBI)
PIK3CA ProteinP42336 (Uniprot-TrEMBL)
PIK3CB ProteinP42338 (Uniprot-TrEMBL)
PIK3R1 ProteinP27986 (Uniprot-TrEMBL)
PIK3R2 ProteinO00459 (Uniprot-TrEMBL)
PIP3 AKT2 complexComplexREACT_4871 (Reactome)
PIP3 PDK1 complexComplexREACT_5409 (Reactome)
PIP3 Phosphorylated PKB complexComplexREACT_3373 (Reactome)
PIP3 MetaboliteCHEBI:16618 (ChEBI)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PKB PKB RegulatorComplexREACT_4747 (Reactome)
PKB regulatorProteinREACT_5778 (Reactome)
RAF/MAP kinase cascadePathwayREACT_634 (Reactome) 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.
RHEB ProteinQ15382 (Uniprot-TrEMBL)
RPS6KB1ProteinP23443 (Uniprot-TrEMBL)
RPS6ProteinP62753 (Uniprot-TrEMBL)
RPTOR ProteinQ8N122 (Uniprot-TrEMBL)
RPTORProteinQ8N122 (Uniprot-TrEMBL)
Rheb GDPComplexREACT_7464 (Reactome)
Rheb GTPComplexREACT_7765 (Reactome)
SHC1 ProteinP29353-1 (Uniprot-TrEMBL)
SHC1-1ProteinP29353-3 (Uniprot-TrEMBL)
SHC1-2 ProteinP29353-2 (Uniprot-TrEMBL)
SHC1ProteinREACT_150482 (Reactome)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
THEM4 ProteinQ5T1C6 (Uniprot-TrEMBL)
TRIB3 ProteinQ96RU7 (Uniprot-TrEMBL)
TSC1 Inhibited TSC2-1-PComplexREACT_7650 (Reactome)
TSC1 TSC2ComplexREACT_7850 (Reactome)
TSC1 ProteinQ92574 (Uniprot-TrEMBL)
TSC2 ProteinP49815 (Uniprot-TrEMBL)
TSC2ProteinP49815 (Uniprot-TrEMBL)
eIF4E 4E-BP1-PComplexREACT_7838 (Reactome)
eIF4E 4E-BPComplexREACT_3978 (Reactome)
p-5S-RPS6ProteinP62753 (Uniprot-TrEMBL)
p-6Y-IRS1 ProteinP35568 (Uniprot-TrEMBL)
p-IRS1,2ProteinREACT_4523 (Reactome)
p-S1108,S1148,S1192-EIF4G1ProteinQ04637 (Uniprot-TrEMBL)
p-S318-PDE3BProteinQ13370 (Uniprot-TrEMBL)
p-S366-EEF2KProteinO00418 (Uniprot-TrEMBL)
p-S371,T389-RPS6KB1ProteinP23443 (Uniprot-TrEMBL)
p-S422-EIF4BProteinP23588 (Uniprot-TrEMBL)
p-S722,S792-RPTOR-1ProteinQ8N122-1 (Uniprot-TrEMBL)
p-S939,S1130,T1462-TSC2 ProteinP49815 (Uniprot-TrEMBL)
p-S939,S1130,T1462-TSC2ProteinP49815 (Uniprot-TrEMBL)
p-SHCProteinREACT_12146 (Reactome)
p-T37,T46-EIF4EBP1 ProteinQ13541 (Uniprot-TrEMBL)
p-T37,T46-EIF4EBP1ProteinQ13541 (Uniprot-TrEMBL)
p-Y-DOK1 ProteinQ99704 (Uniprot-TrEMBL)
p-Y-IRS1 ProteinP35568 (Uniprot-TrEMBL)
p-Y-IRS2 ProteinQ9Y4H2 (Uniprot-TrEMBL)
p-Y-IRS4 ProteinO14654 (Uniprot-TrEMBL)
p-Y-SHC1 ProteinP29353 (Uniprot-TrEMBL)
p-Y-SHC2 ProteinP98077 (Uniprot-TrEMBL)
p-Y-SHC3 ProteinQ92529 (Uniprot-TrEMBL)
p-Y1161,Y1165,Y1166-IGF1RProteinP08069 (Uniprot-TrEMBL)
p-Y194,Y195,Y272-SHC1-1ProteinP29353-3 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2 ProteinP29353-2 (Uniprot-TrEMBL)
p-Y349,Y350,Y427-SHC1 ProteinP29353-1 (Uniprot-TrEMBL)
p21 RAS GDPComplexREACT_2657 (Reactome)
p21 RAS GTPComplexREACT_4782 (Reactome)
phospho-IRS PI3KComplexREACT_3175 (Reactome)
phospho-IRSProteinREACT_4422 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
3',5'-Cyclic AMPREACT_325 (Reactome)
ADPArrowREACT_150135 (Reactome)
ADPArrowREACT_150227 (Reactome)
ADPArrowREACT_150288 (Reactome)
ADPArrowREACT_1878 (Reactome)
ADPArrowREACT_244 (Reactome)
ADPArrowREACT_6725 (Reactome)
ADPArrowREACT_6778 (Reactome)
ADPArrowREACT_6870 (Reactome)
ADPArrowREACT_6873 (Reactome)
ADPArrowREACT_6883 (Reactome)
ADPArrowREACT_6912 (Reactome)
ADPArrowREACT_6948 (Reactome)
ADPArrowREACT_6952 (Reactome)
ADPArrowREACT_908 (Reactome)
ATPREACT_150135 (Reactome)
ATPREACT_150227 (Reactome)
ATPREACT_150288 (Reactome)
ATPREACT_1878 (Reactome)
ATPREACT_244 (Reactome)
ATPREACT_6725 (Reactome)
ATPREACT_6778 (Reactome)
ATPREACT_6870 (Reactome)
ATPREACT_6873 (Reactome)
ATPREACT_6883 (Reactome)
ATPREACT_6912 (Reactome)
ATPREACT_6948 (Reactome)
ATPREACT_6952 (Reactome)
ATPREACT_908 (Reactome)
Activated PI3Kmim-catalysisREACT_244 (Reactome)
Activated mTORC1mim-catalysisREACT_6873 (Reactome)
Activated mTORC1mim-catalysisREACT_6948 (Reactome)
EEF2KREACT_6883 (Reactome)
EIF4BREACT_6778 (Reactome)
EIF4EArrowREACT_6742 (Reactome)
EIF4G1REACT_6870 (Reactome)
GDPArrowREACT_1672 (Reactome)
GDPArrowREACT_2010 (Reactome)
GDPArrowREACT_6895 (Reactome)
GRB2

SOS

IRS-P		mim-catalysisREACT_1672 (Reactome)
GRB2

SOS

Phospho-SHC		mim-catalysisREACT_2010 (Reactome)
GRB2 SOS1REACT_176 (Reactome)
GRB2 SOS1REACT_646 (Reactome)
GTPREACT_1672 (Reactome)
GTPREACT_2010 (Reactome)
GTPREACT_6895 (Reactome)
H2OREACT_325 (Reactome)
IGF1/2 IGF1RREACT_150288 (Reactome)
IGF1/2 IGF1Rmim-catalysisREACT_150288 (Reactome)
IGF1/2

p-IGF1R

IRS1/2/4		REACT_150135 (Reactome)
IGF1/2

p-IGF1R

IRS1/2/4		mim-catalysisREACT_150135 (Reactome)
IGF1/2

p-IGF1R

SHC1		REACT_150227 (Reactome)
IGF1/2

p-IGF1R

SHC1		mim-catalysisREACT_150227 (Reactome)
IGF1/2

p-IGF1R

p-IRS1/2/4		ArrowREACT_150135 (Reactome)
IGF1/2

p-IGF1R

p-SHC1		ArrowREACT_150227 (Reactome)
IGF1/2 p-IGF1RArrowREACT_150288 (Reactome)
IGF1/2 p-IGF1RREACT_150315 (Reactome)
IGF1/2 p-IGF1RREACT_150340 (Reactome)
IGF1/2 p-IGF1RREACT_150430 (Reactome)
IGF1/2REACT_150464 (Reactome)
IGF1RREACT_150464 (Reactome)
IRS1/4REACT_150315 (Reactome)
IRS2REACT_150340 (Reactome)
MLST8REACT_6851 (Reactome)
MTORREACT_6851 (Reactome)
PDE3BREACT_1878 (Reactome)
PDPK1REACT_260 (Reactome)
PI3KREACT_537 (Reactome)
PIP3 AKT2 complexArrowREACT_1622 (Reactome)
PIP3 AKT2 complexREACT_908 (Reactome)
PIP3 PDK1 complexmim-catalysisREACT_908 (Reactome)
PIP3 Phosphorylated PKB complexArrowREACT_908 (Reactome)
PIP3 Phosphorylated PKB complexmim-catalysisREACT_1878 (Reactome)
PIP3 Phosphorylated PKB complexmim-catalysisREACT_6725 (Reactome)
PIP3 Phosphorylated PKB complexmim-catalysisREACT_6952 (Reactome)
PIP3ArrowREACT_244 (Reactome)
PIP3REACT_1622 (Reactome)
PIP3REACT_260 (Reactome)
PIREACT_244 (Reactome)
PKB PKB RegulatorREACT_1622 (Reactome)
PKB regulatorArrowREACT_1622 (Reactome)
REACT_150135 (Reactome) Phosphorylated IGF1R phosphorylates IRS1 (Siemeister et al. 1995, Xu et al. 1995, Takahashi et al. 1997, Rakatzi et al. 2006), IRS2 (Kim et al. 1998, Kim et al. 2004), and IRS4 (Fantin et al.1998, Karas et al. 2001, Cuevas et al. 2007) on numerous tyrosine residues. IRS4 is phosphorylated by IGF1R in HEK cells but not in primary muscle cells (Fantin et al. 1998, Schreyer et al. 2003). The phosphotyrosine resideus create binding sites for downstream effectors such as GRB2:SOS and PI3K.
REACT_150227 (Reactome) The phosphorylated IGF1R phosphorylates SHC1 (Giorgetti et al. 1994, Hernandez-Sanchez et al. 1995, Kim et al. 1998). Phosphorylation of SHC1 is sustained whereas phosphorylation of IRS2 by IGF1R is transient (Kim et al. 1998).
REACT_150288 (Reactome) The beta peptide of the type 1 insulin-like growth factor (IGF1R) spans the plasma membrane and trans-autophosphorylates tyrosine residues in response to binding of either IGF1 or IGF2 by the extracellular alpha peptide (LeBon et al. 1986, Yu et al. 1986, Doronio et al. 1990, Hernandez-Sanchez et al. 1995, Alvino et al. 2001).
REACT_150315 (Reactome) IRS1 binds the NPEY-juxtamembrane motif of phosphorylated IGF1R (Craparo et al. 1995, He et al. 1995, Huang et al. 2001). IRS4 is also involved in signaling by IGF1R and is presumed to bind phosphorylated IGF1R in the same way as IRS1 (Qu et al. 1999, Cuevas et al. 2007). IRS1 and IRS4 are located at the plasma membrane (Karlsson et al. 2004, Fantin et al. 1998).
REACT_150340 (Reactome) IRS2 binds the NPEY-juxtamembrane motif of phosphorylated IGF1R (He et al. 1996, Kim et al. 1998). IRS2 is cytosolic while IRS1 and IRS4 are located in the plasma membrane.
REACT_150430 (Reactome) SHC1 binds the NPEY-juxtamembrane motif of the phosphorylated insulin-like growth factor receptor (IGF1R) (Giorgetti et al. 1994, Tartare-Deckert et al. 1995).
REACT_150464 (Reactome) Either IGF1 (IGF-I) or IGF2 (IGF-II) can bind the type 1 insulin-like growth factor receptor (IGF1R) (Casella et al. 1986, LeBon et al. 1986, Maly and Luthi 1986, Cacieri et al. 1988, Steele-Perkins et al. 1988, Burgisser et al. 1991, Germain-Lee et al. 1992, Keyhanfar et al. 2007, Alvino et al. 2009, Alvino et al. 2011). IGF1R has similar affinities for IGF1 and IGF2 (Casella et al. 1986, Steele-Perkins et al. 1988). The binding sites for IGF1 and IGF2 are in a similar location on the alpha peptide of IGF1R but there are some differences in which residues of IGF1R interact with IGF1 vs. IGF2 (Keyhanfar et al. 2007, Alvino et al. 2009, Alvino et al. 2011).
REACT_1622 (Reactome) At the beginning of this reaction, 1 molecule of 'PKB:PKB Regulator', and 1 molecule of 'Phosphatidylinositol-3,4,5-trisphosphate' are present. At the end of this reaction, 1 molecule of 'PKB regulator', and 1 molecule of 'PIP3:PKB complex ' are present.

This reaction takes place in the 'cell'.

REACT_1672 (Reactome) SOS promotes the formation of GTP-bound RAS, thus activating this protein. RAS activation results in activation of the protein kinases RAF1, B-Raf, and MAP-ERK kinase kinase (MEKK), and the catalytic subunit of PI3K, as well as of a series of RALGEFs. The activation cycle of RAS GTPases is regulated by their interaction with specific guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). GEFs promote activation by inducing the release of GDP, whereas GAPs inactivate RAS-like proteins by stimulating their intrinsic GTPase activity. NGF-induced RAS activation via SHC-GRB2-SOS is maximal at 2 min but it is no longer detected after 5 min. Therefore, the transient activation of RAS obtained through SHC-GRB2-SOS is insufficient for the prolonged activation of ERKs found in NGF-treated cells.

REACT_176 (Reactome) Tyrosine receptor kinase stimulation phosphorylates Shc which recruits the SH2 domain of the adaptor protein GRB2, which is complexed with SOS, an exchange factor for p21ras and RAC, through its SH3 domain. Besides SOS, the GRB2 SH3 domain can associate with other intracellular targets, including GAB1. Erk and Rsk mediated phosphorylation results in dissociation of the SOS-GRB2 complex. This may explain why Erk activation through Shc and SOS-GRB2 is transient. Inactive p21ras-GDP is found anchored to the plasma membrane by a farnesyl residue. As Shc is phosphorylated by the the stimulated receptor near to the plasma membrane, the SOS-GRB2:Shc interaction brings the SOS enzyme into close proximity to p21ras.
REACT_1878 (Reactome) At the beginning of this reaction, 2 molecules of 'ATP', and 1 molecule of 'PDE3B' are present. At the end of this reaction, 1 molecule of 'Phosphorylated PDE3B', and 2 molecules of 'ADP' are present.

This reaction is mediated by the 'kinase activity' of 'PIP3:Phosphorylated PKB complex'.

REACT_2010 (Reactome) SOS promotes the formation of GTP-bound RAS, thus activating this protein. RAS activation results in activation of the protein kinases RAF1, B-Raf, and MAP-ERK kinase kinase (MEKK), and the catalytic subunit of PI3K, as well as of a series of RALGEFs. The activation cycle of RAS GTPases is regulated by their interaction with specific guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). GEFs promote activation by inducing the release of GDP, whereas GAPs inactivate RAS-like proteins by stimulating their intrinsic GTPase activity. NGF-induced RAS activation via SHC-GRB2-SOS is maximal at 2 min but it is no longer detected after 5 min. Therefore, the transient activation of RAS obtained through SHC-GRB2-SOS is insufficient for the prolonged activation of ERKs found in NGF-treated cells.

REACT_244 (Reactome) At the beginning of this reaction, 1 molecule of 'Phosphatidyl-myo-inositol 4,5-bisphosphate', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'Phosphatidylinositol-3,4,5-trisphosphate', and 1 molecule of 'ADP' are present.

This reaction takes place in the 'cell' and is mediated by the 'kinase activity' of 'phospho-IRS:PI3K'.

REACT_260 (Reactome) At the beginning of this reaction, 1 molecule of '3-phosphoinositide dependent protein kinase-1 ', and 1 molecule of 'Phosphatidylinositol-3,4,5-trisphosphate' are present. At the end of this reaction, 1 molecule of 'PIP3:PDK complex [plasma membrane]' is present.

This reaction takes place in the 'cell'.

REACT_325 (Reactome) At the beginning of this reaction, 1 molecule of '3',5'-Cyclic AMP' is present. At the end of this reaction, 1 molecule of 'AMP' is present.

This reaction is mediated by the 'hydrolase activity' of 'Phosphorylated PDE3B'.

REACT_537 (Reactome) IRS1, IRS2 and IRS3 are all known to bind the regulatory subunit of PI3K via its SH2 domain, an interaction that itself activates the kinase activity of the PI3K catalytic subunit.
REACT_646 (Reactome) Inactive p21ras-GDP is found anchored to the plasma membrane by a farnesyl residue.
Insulin stimulation results in phosphorylation of IRS1/2 on tyrosine residues (Y). GRB2 binds the phosphotyrosine residues of IRS via its SH2 domain. As IRS is phosphorylated by the insulin receptor near to the plasma membrane, the SOS-GRB2:IRS interaction brings the SOS enzyme into close proximity to p21ras.
REACT_6725 (Reactome) At the beginning of this reaction, 3 molecules of 'ATP', and 1 molecule of 'TSC2-1' are present. At the end of this reaction, 3 molecules of 'ADP', and 1 molecule of 'Inhibited TSC2-1-P at Ser 939, 1130 and Thr 1462' are present.

This reaction is mediated by the 'kinase activity' of 'PIP3:Phosphorylated PKB complex'.

REACT_6742 (Reactome) At the beginning of this reaction, 1 molecule of 'eIF4E:4E-BP1-P' is present. At the end of this reaction, 1 molecule of '4E-BP1-P', and 1 molecule of 'eIF4E' are present.

This reaction takes place in the 'cytosol'.

REACT_6778 (Reactome) eIF4B is a physiologically relevant target of S6K1. Once phosphorylated and activated by S6K1, eIF4B specifically stimulates the ATPase and RNA helicase activities of eIF4A.
REACT_6851 (Reactome) mTOR forms a functional protein complex with at least two proteins: Raptor (Regulated Associated Protein of mTOR) and mLst8. This complex is called mammalian TOR complex 1 (mTORC1). Raptor serves as a scaffolding protein to bridge the interaction between mTOR and its substrates. mLst8 enhances the association of mTOR with Raptor. [Rheb:GTP] binds and activates mTORC1. Besides binding directly to mTOR, Rheb can also bind to Raptor and mLst8 (PMIDs 15854902, 15755954 and 12150926).
REACT_6870 (Reactome) At the beginning of this reaction, 3 molecules of 'ATP', and 1 molecule of 'eIF4G' are present. At the end of this reaction, 3 molecules of 'ADP', and 1 molecule of 'eIF4G-P' are present.

This reaction takes place in the 'cytosol' and is mediated by the 'kinase activity' of 'S6K1-P'.

REACT_6873 (Reactome) At the beginning of this reaction, 2 molecules of 'ATP', and 1 molecule of 'eIF4E:4E-BP' are present. At the end of this reaction, 1 molecule of 'eIF4E:4E-BP1-P', and 2 molecules of 'ADP' are present.

This reaction is mediated by the 'kinase activity' of 'Activated mTORC1'.

REACT_6883 (Reactome) Phosphorylation of eEF2 kinase by S6K1-P results in decreased activity of this kinase. eEF2 kinase normally phosphorylates and deactivates eEF2, preventing its binding to the ribosome.
REACT_6895 (Reactome) Rheb is a GTP binding protein that exhibits GTPase activity. GDP is exchanged for GTP in the [Rheb:GDP] complex to form [Rheb:GTP], which binds and activates the mTORC1 complex. This exchange is catalysed by an as yet unidentified guanine exchange factor (GEF) (PMIDs 15951850 and 15755954).
REACT_6912 (Reactome) Once phosphorylated, S6K1-P phosphorylates and activates ribosomal protein S6 (rpS6), which in turn selectively increases the translation of 5’TOP mRNAs. These mRNAs encode exclusively for components of the translation machinery (PMID 15809305).
REACT_6948 (Reactome) S6K1 contains a TOS motif. mTORC1 requires an intact TOS motif to bind and phosphorylate S6K1 (PMID 15809305).
REACT_6952 (Reactome) At the beginning of this reaction, 3 molecules of 'ATP', and 1 molecule of 'TSC1:TSC2' are present. At the end of this reaction, 3 molecules of 'ADP', and 1 molecule of 'TSC1:Inhibited TSC2-1-P' are present.

This reaction is mediated by the 'kinase activity' of 'PIP3:Phosphorylated PKB complex'.

REACT_908 (Reactome) At the beginning of this reaction, 2 molecules of 'ATP', and 1 molecule of 'PIP3:PKB complex ' are present. At the end of this reaction, 1 molecule of 'PIP3:Phosphorylated PKB complex', and 2 molecules of 'ADP' are present.

This reaction takes place on the 'plasma membrane' and is mediated by the 'kinase activity' of 'PIP3:PDK complex [plasma membrane]'.

RPS6KB1REACT_6948 (Reactome)
RPS6REACT_6912 (Reactome)
RPTORREACT_6851 (Reactome)
Rheb GDPREACT_6895 (Reactome)
Rheb GTPArrowREACT_6895 (Reactome)
Rheb GTPREACT_6851 (Reactome)
SHC1REACT_150430 (Reactome)
TSC1 Inhibited TSC2-1-PArrowREACT_6952 (Reactome)
TSC1 TSC2REACT_6952 (Reactome)
TSC2REACT_6725 (Reactome)
eIF4E 4E-BP1-PArrowREACT_6873 (Reactome)
eIF4E 4E-BPREACT_6873 (Reactome)
p-5S-RPS6ArrowREACT_6912 (Reactome)
p-IRS1,2REACT_646 (Reactome)
p-S1108,S1148,S1192-EIF4G1ArrowREACT_6870 (Reactome)
p-S318-PDE3BArrowREACT_1878 (Reactome)
p-S318-PDE3Bmim-catalysisREACT_325 (Reactome)
p-S366-EEF2KArrowREACT_6883 (Reactome)
p-S371,T389-RPS6KB1ArrowREACT_6948 (Reactome)
p-S371,T389-RPS6KB1mim-catalysisREACT_6778 (Reactome)
p-S371,T389-RPS6KB1mim-catalysisREACT_6870 (Reactome)
p-S371,T389-RPS6KB1mim-catalysisREACT_6883 (Reactome)
p-S371,T389-RPS6KB1mim-catalysisREACT_6912 (Reactome)
p-S422-EIF4BArrowREACT_6778 (Reactome)
p-S722,S792-RPTOR-1TBarREACT_6948 (Reactome)
p-S939,S1130,T1462-TSC2ArrowREACT_6725 (Reactome)
p-SHCREACT_176 (Reactome)
p-T37,T46-EIF4EBP1ArrowREACT_6742 (Reactome)
p21 RAS GDPREACT_1672 (Reactome)
p21 RAS GDPREACT_2010 (Reactome)
p21 RAS GTPArrowREACT_1672 (Reactome)
p21 RAS GTPArrowREACT_2010 (Reactome)
phospho-IRSREACT_537 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2677"
Personal tools