KEGG PATHWAY: mdo04012

PATHWAY: mdo04012

Entry

mdo04012 Pathway

Name

ErbB signaling pathway - Monodelphis domestica (opossum)

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

mdo04012

ErbB signaling pathway

Organism

Monodelphis domestica (opossum) [GN:mdo]

Gene

100619143	pro-epidermal growth factor-like; K04357 epidermal growth factor [KO:K04357]
100032790	protransforming growth factor alpha-like; K08774 transforming growth factor, alpha [KO:K08774]
100023978	amphiregulin-like; K09782 amphiregulin [KO:K09782]
100029625	EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100017172	ERBB2; v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) [KO:K05083] [EC:2.7.10.1]
100032696	PLCG1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
100027579	PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
100011784	calcium/calmodulin-dependent protein kinase type II subunit delta-like; K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] [KO:K04515] [EC:2.7.11.17]
100010898	CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
100024521	CAMK2B; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
100028973	calcium/calmodulin-dependent protein kinase type II subunit alpha-like; K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] [KO:K04515] [EC:2.7.11.17]
100013346	protein kinase C beta type-like; K02677 classical protein kinase C [EC:2.7.11.13] [KO:K02677] [EC:2.7.11.13]
100024674	protein kinase C alpha type-like; K02677 classical protein kinase C [EC:2.7.11.13] [KO:K02677] [EC:2.7.11.13]
100031184	e3 ubiquitin-protein ligase CBL-like; K04707 E3 ubiquitin-protein ligase CBL [EC:6.3.2.19] [KO:K04707] [EC:6.3.2.19]
100023698	signal transduction protein CBL-C-like; K04707 E3 ubiquitin-protein ligase CBL [EC:6.3.2.19] [KO:K04707] [EC:6.3.2.19]
100011932	CBLB; Cbl proto-oncogene, E3 ubiquitin protein ligase B [KO:K04707] [EC:6.3.2.19]
100012174	signal transducer and activator of transcription 5B-like; K11223 signal transducer and activator of transcription 5A [KO:K11223]
100011470	STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
100029391	proto-oncogene tyrosine-protein kinase Src-like; K05704 tyrosine-protein kinase Src [EC:2.7.10.2] [KO:K05704] [EC:2.7.10.2]
100027188	PTK2; PTK2 protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
100012317	adapter molecule crk-like; K04438 proto-oncogene C-crk [KO:K04438]
100015312	crk-like protein-like; K04438 proto-oncogene C-crk [KO:K04438]
100619549	ABL1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
100016915	ABL2; v-abl Abelson murine leukemia viral oncogene homolog 2 [KO:K08887] [EC:2.7.10.2]
100016740	NCK1; NCK adaptor protein 1 [KO:K07365]
100014693	NCK2; NCK adaptor protein 2 [KO:K07365]
100018336	serine/threonine-protein kinase PAK 1-like; K04409 p21-activated kinase 1 [EC:2.7.11.1] [KO:K04409] [EC:2.7.11.1]
100015796	PAK2; p21 protein (Cdc42/Rac)-activated kinase 2 [KO:K04410] [EC:2.7.11.1]
100012727	serine/threonine-protein kinase PAK 3-like; K05733 p21-activated kinase 3 [EC:2.7.11.1] [KO:K05733] [EC:2.7.11.1]
100013977	PAK4; p21 protein (Cdc42/Rac)-activated kinase 4 [KO:K05734] [EC:2.7.11.1]
100033279	serine/threonine-protein kinase PAK 7-like; K05736 p21-activated kinase 7 [EC:2.7.11.1] [KO:K05736] [EC:2.7.11.1]
100019828	MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
100026752	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]
100014343	MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100028089	MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100618895	MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100018774	transcription factor AP-1-like; K04448 transcription factor AP-1 [KO:K04448]
100617037	ETS domain-containing protein Elk-1-like; K04375 ETS domain-containing protein Elk-1 [KO:K04375]
100026152	proheparin-binding EGF-like growth factor-like; K08523 heparin-binding EGF-like growth factor [KO:K08523]
100023929	proepiregulin-like; K09784 epiregulin [KO:K09784]
100028103	ERBB3; v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) [KO:K05084] [EC:2.7.10.1]
100028072	receptor tyrosine-protein kinase erbB-3-like; K05084 receptor tyrosine-protein kinase erbB-3 [EC:2.7.10.1] [KO:K05084] [EC:2.7.10.1]
100019114	NRG1; neuregulin 1 [KO:K05455]
100020721	pro-neuregulin-2; K05456 neuregulin 2 [KO:K05456]
100014865	ERBB4; v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) [KO:K05085] [EC:2.7.10.1]
100031128	SHC4; SHC (Src homology 2 domain containing) family, member 4 [KO:K06279]
100016090	SHC1; SHC (Src homology 2 domain containing) transforming protein 1 [KO:K06279]
100024603	SHC3; SHC (Src homology 2 domain containing) transforming protein 3 [KO:K06279]
100022894	growth factor receptor-bound protein 2-like; K04364 growth factor receptor-binding protein 2 [KO:K04364]
100618058	son of sevenless homolog 1-like; K03099 son of sevenless [KO:K03099]
100029256	SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
100032921	GTPase HRas-like; K02833 GTPase HRas [KO:K02833]
100009992	GTPase KRas-like; K07827 GTPase KRas [KO:K07827]
554186	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
554197	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
100024057	BRAF; v-raf murine sarcoma viral oncogene homolog B1 [KO:K04365] [EC:2.7.11.1]
100015410	RAF proto-oncogene serine/threonine-protein kinase-like; K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04366] [EC:2.7.11.1]
100018410	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100018044	dual specificity mitogen-activated protein kinase kinase 2-like; K04369 mitogen-activated protein kinase kinase 2 [EC:2.7.12.2] [KO:K04369] [EC:2.7.12.2]
100028096	mitogen-activated protein kinase 1-like; K04371 extracellular signal-regulated kinase 1/2 [EC:2.7.11.24] [KO:K04371] [EC:2.7.11.24]
100012916	MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100032344	myc proto-oncogene protein-like; K04377 Myc proto-oncogene protein [KO:K04377]
100019200	GAB1; GRB2-associated binding protein 1 [KO:K09593]
100013291	NRG3; neuregulin 3 [KO:K05457]
100025638	pro-neuregulin-4; K05458 neuregulin 4 [KO:K05458]
100009879	phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
100010412	phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
100017332	phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
100019317	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
100012464	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
100032726	phosphatidylinositol 3-kinase regulatory subunit beta-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
100014564	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
100019947	RAC-alpha serine/threonine-protein kinase-like; K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04456] [EC:2.7.11.1]
100027373	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
100014573	ribosomal protein S6 kinase beta-2-like; K04688 p70 ribosomal S6 kinase [EC:2.7.11.1] [KO:K04688] [EC:2.7.11.1]
100010269	ribosomal protein S6 kinase beta-1-like; K04688 p70 ribosomal S6 kinase [EC:2.7.11.1] [KO:K04688] [EC:2.7.11.1]
100029774	eukaryotic translation initiation factor 4E-binding protein 1-like; K07205 eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
100031246	bcl2 antagonist of cell death-like; K02158 BCL2-antagonist of cell death [KO:K02158]
100012447	GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100029103	cyclin-dependent kinase inhibitor 1-like; K06625 cyclin-dependent kinase inhibitor 1A [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 (80)   
   KEGG GENES (80)   
All databases (82)   

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