KEGG PATHWAY: mcc04012

PATHWAY: mcc04012

Entry

mcc04012 Pathway

Name

ErbB signaling pathway - Macaca mulatta (rhesus monkey)

Description

The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. Similarly, the phosphatidylinositol-3-kinase (PI-3K) pathway is directly or indirectly activated by most ErbBs. Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase.

Class

Environmental Information Processing; Signal transduction

Pathway map

mcc04012

ErbB signaling pathway

Organism

Macaca mulatta (rhesus monkey) [GN:mcc]

Gene

698619	EGF; epidermal growth factor [KO:K04357]
613031	TGFA; transforming growth factor, alpha [KO:K08774]
702396	AREGB; amphiregulin B [KO:K09782]
613027	EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
697573	ERBB2; v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) [KO:K05083] [EC:2.7.10.1]
697069	PLCG1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
714173	PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
705980	CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
702504	CAMK2D; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
706977	calcium/calmodulin-dependent protein kinase type II subunit beta-like; K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] [KO:K04515] [EC:2.7.11.17]
701195	PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
720263	PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
718412	PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
713112	CBLC; Cbl proto-oncogene, E3 ubiquitin protein ligase C [KO:K04707] [EC:6.3.2.19]
704311	CBL; Cbl proto-oncogene, E3 ubiquitin protein ligase [KO:K04707] [EC:6.3.2.19]
703879	e3 ubiquitin-protein ligase CBL-B-like; K04707 E3 ubiquitin-protein ligase CBL [EC:6.3.2.19] [KO:K04707] [EC:6.3.2.19]
574129	STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
709760	STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
701057	SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [KO:K05704] [EC:2.7.10.2]
700634	PTK2; PTK2 protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
696584	CRKL; v-crk sarcoma virus CT10 oncogene homolog (avian)-like [KO:K04438]
701185	adapter molecule crk-like; K04438 proto-oncogene C-crk [KO:K04438]
722449	ABL1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
717037	ABL2; v-abl Abelson murine leukemia viral oncogene homolog 2 [KO:K08887] [EC:2.7.10.2]
716807	NCK1; NCK adaptor protein 1 [KO:K07365]
713287	NCK2; NCK adaptor protein 2 [KO:K07365]
698585	PAK1; p21 protein (Cdc42/Rac)-activated kinase 1 [KO:K04409] [EC:2.7.11.1]
710314	PAK2; p21 protein (Cdc42/Rac)-activated kinase 2 [KO:K04410] [EC:2.7.11.1]
706217	PAK3; p21 protein (Cdc42/Rac)-activated kinase 3 [KO:K05733] [EC:2.7.11.1]
696676	PAK4; p21 protein (Cdc42/Rac)-activated kinase 4 [KO:K05734] [EC:2.7.11.1]
701589	PAK6; p21 protein (Cdc42/Rac)-activated kinase 6 [KO:K05735] [EC:2.7.11.1]
719458	PAK7; p21 protein (Cdc42/Rac)-activated kinase 7 [KO:K05736] [EC:2.7.11.1]
718155	MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
710077	dual specificity mitogen-activated protein kinase kinase 7-like; K04431 mitogen-activated protein kinase kinase 7 [EC:2.7.12.2] [KO:K04431] [EC:2.7.12.2]
699736	MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
711115	MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
716452	JUN; jun proto-oncogene [KO:K04448]
722713	ELK1; ELK1, member of ETS oncogene family pseudogene [KO:K04375]
712610	ELK1; ELK1, member of ETS oncogene family [KO:K04375]
702178	BTC; betacellulin [KO:K09783]
695559	HBEGF; heparin-binding EGF-like growth factor [KO:K08523]
702502	EREG; epiregulin [KO:K09784]
711407	ERBB3; v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) [KO:K05084] [EC:2.7.10.1]
696275	NRG1; neuregulin 1 [KO:K05455]
713584	ERBB4; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:2.7.10.1]
574275	SHC3; SHC (Src homology 2 domain containing) transforming protein 3 [KO:K06279]
718982	SHC1; SHC (Src homology 2 domain containing) transforming protein 1 [KO:K06279]
714611	SHC4; SHC (Src homology 2 domain containing) family, member 4 [KO:K06279]
721021	SHC2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K06279]
702041	growth factor receptor-bound protein 2-like; K04364 growth factor receptor-binding protein 2 [KO:K04364]
713777	SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
705601	SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
698830	HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
707977	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
709089	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
707169	ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
693554	serine/threonine-protein kinase B-raf-like; K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04365] [EC:2.7.11.1]
694725	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
710415	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
721821	MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
698569	MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
708938	MAPK3; mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
694626	MYC; v-myc myelocytomatosis viral oncogene homolog (avian) [KO:K04377]
700367	GAB1; GRB2-associated binding protein 1 [KO:K09593]
699268	NRG3; neuregulin 3 [KO:K05457]
707378	NRG4; neuregulin 4 [KO:K05458]
698857	PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
716098	PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
709959	PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
707310	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
719367	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
722027	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
698996	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
714717	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
697747	AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
700591	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
721731	RPS6KB2; ribosomal protein S6 kinase, 70kDa, polypeptide 2 [KO:K04688] [EC:2.7.11.1]
711979	RPS6KB1; ribosomal protein S6 kinase, 70kDa, polypeptide 1 [KO:K04688] [EC:2.7.11.1]
703628	EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
717740	BAD; BCL2-associated agonist of cell death [KO:K02158]
713114	GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
719199	CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]

Compound

C00076	Calcium cation
C00165	Diacylglycerol
C01245	D-myo-Inositol 1,4,5-trisphosphate
C05981	Phosphatidylinositol-3,4,5-trisphosphate

Reference

PMID:14967450

Authors

Marmor MD, Skaria KB, Yarden Y.

Title

Signal transduction and oncogenesis by ErbB/HER receptors.

Journal

Int J Radiat Oncol Biol Phys 58:903-13 (2004)

Reference

PMID:11252954

Authors

Yarden Y, Sliwkowski MX.

Title

Untangling the ErbB signalling network.

Journal

Nat Rev Mol Cell Biol 2:127-37 (2001)

Reference

PMID:16829981

Authors

Citri A, Yarden Y.

Title

EGF-ERBB signalling: towards the systems level.

Journal

Nat Rev Mol Cell Biol 7:505-16 (2006)

Reference

PMID:17000658

Authors

Scaltriti M, Baselga J.

Title

The epidermal growth factor receptor pathway: a model for targeted therapy.

Journal

Clin Cancer Res 12:5268-72 (2006)

Reference

PMID:16377102

Authors

Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS.

Title

Epidermal growth factor receptor (EGFR) signaling in cancer.

Journal

Gene 366:2-16 (2006)

Reference

PMID:14744244

Authors

Holbro T, Hynes NE.

Title

ErbB receptors: directing key signaling networks throughout life.

Journal

Annu Rev Pharmacol Toxicol 44:195-217 (2004)

Reference

PMID:12851486

Authors

Liang J, Slingerland JM.

Title

Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.

Journal

Cell Cycle 2:339-45 (2003)

Reference

PMID:15864276

Authors

Hynes NE, Lane HA.

Title

ERBB receptors and cancer: the complexity of targeted inhibitors.

Journal

Nat Rev Cancer 5:341-54 (2005)

Reference

PMID:16729045

Authors

Oda K, Matsuoka Y, Funahashi A, Kitano H.

Title

A comprehensive pathway map of epidermal growth factor receptor signaling.

Journal

Mol Syst Biol 1:2005.0010 (2005)

Reference

PMID:16729043

Authors

Schulze WX, Deng L, Mann M.

Title

Phosphotyrosine interactome of the ErbB-receptor kinase family.

Journal

Mol Syst Biol 1:2005.0008 (2005)

Reference

PMID:10880430

Authors

Olayioye MA, Neve RM, Lane HA, Hynes NE.

Title

The ErbB signaling network: receptor heterodimerization in development and cancer.

Journal

EMBO J 19:3159-67 (2000)

Reference

PMID:9872057

Authors

McCarty JH.

Title

The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.

Journal

Bioessays 20:913-21 (1998)

Reference

PMID:15863494

Authors

Clark DE, Williams CC, Duplessis TT, Moring KL, Notwick AR, Long W, Lane WS, Beuvink I, Hynes NE, Jones FE.

Title

ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.

Journal

J Biol Chem 280:24175-80 (2005)

Reference

PMID:10490623

Authors

Muthuswamy SK, Gilman M, Brugge JS.

Title

Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.

Journal

Mol Cell Biol 19:6845-57 (1999)

Reference

PMID:9642287

Authors

Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda M.

Title

Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.

Journal

J Biol Chem 273:17186-91 (1998)

KO pathway

ko04012

All links

Pathway (1)   
   BioSystems (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (82)   
   KEGG GENES (82)   
All databases (84)   

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