KEGG   PATHWAY: mmu04012Help
Entry
mmu04012                    Pathway                                

Name
ErbB signaling pathway - Mus musculus (mouse)
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
BRITE hierarchy
Pathway map
ErbB signaling pathway
mmu04012

All organismsOrtholog table
Organism
Mus musculus (mouse) [GN:mmu]
Gene
13645  
Egf; epidermal growth factor [KO:K04357]
21802  
Tgfa; transforming growth factor alpha [KO:K08774]
11839  
Areg; amphiregulin [KO:K09782]
13649  
Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
13866  
Erbb2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
18803  
Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
234779  
Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
108058  
Camk2d; calcium/calmodulin-dependent protein kinase II, delta [KO:K04515] [EC:2.7.11.17]
12325  
Camk2g; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
12323  
Camk2b; calcium/calmodulin-dependent protein kinase II, beta [KO:K04515] [EC:2.7.11.17]
12322  
Camk2a; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
18750  
Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
18751  
Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
18752  
Prkcg; protein kinase C, gamma [KO:K19663] [EC:2.7.11.13]
12402  
Cbl; Casitas B-lineage lymphoma [KO:K04707] [EC:2.3.2.27]
208650  
Cblb; Casitas B-lineage lymphoma b [KO:K04707] [EC:2.3.2.27]
80794  
Cblc; Casitas B-lineage lymphoma c [KO:K04707] [EC:2.3.2.27]
20850  
Stat5a; signal transducer and activator of transcription 5A [KO:K11223]
20851  
Stat5b; signal transducer and activator of transcription 5B [KO:K11224]
20779  
Src; Rous sarcoma oncogene [KO:K05704] [EC:2.7.10.2]
14083  
Ptk2; PTK2 protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
12928  
Crk; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438]
12929  
Crkl; v-crk avian sarcoma virus CT10 oncogene homolog-like [KO:K04438]
11350  
Abl1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
11352  
Abl2; v-abl Abelson murine leukemia viral oncogene 2 (arg, Abelson-related gene) [KO:K08887] [EC:2.7.10.2]
17973  
Nck1; non-catalytic region of tyrosine kinase adaptor protein 1 [KO:K07365]
17974  
Nck2; non-catalytic region of tyrosine kinase adaptor protein 2 [KO:K19862]
18479  
Pak1; p21 protein (Cdc42/Rac)-activated kinase 1 [KO:K04409] [EC:2.7.11.1]
224105  
Pak2; p21 protein (Cdc42/Rac)-activated kinase 2 [KO:K04410] [EC:2.7.11.1]
18481  
Pak3; p21 protein (Cdc42/Rac)-activated kinase 3 [KO:K05733] [EC:2.7.11.1]
70584  
Pak4; p21 protein (Cdc42/Rac)-activated kinase 4 [KO:K05734] [EC:2.7.11.1]
214230  
Pak6; p21 protein (Cdc42/Rac)-activated kinase 6 [KO:K05735] [EC:2.7.11.1]
241656  
Pak7; p21 protein (Cdc42/Rac)-activated kinase 7 [KO:K05736] [EC:2.7.11.1]
26398  
Map2k4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
26400  
Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
26419  
Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  
Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  
Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
16476  
Jun; jun proto-oncogene [KO:K04448]
13712  
Elk1; ELK1, member of ETS oncogene family [KO:K04375]
12223  
Btc; betacellulin, epidermal growth factor family member [KO:K09783]
15200  
Hbegf; heparin-binding EGF-like growth factor [KO:K08523]
13874  
Ereg; epiregulin [KO:K09784]
13867  
Erbb3; erb-b2 receptor tyrosine kinase 3 [KO:K05084] [EC:2.7.10.1]
211323  
Nrg1; neuregulin 1 [KO:K05455]
Nrg2; neuregulin 2 [KO:K05456]
13869  
Erbb4; erb-b2 receptor tyrosine kinase 4 [KO:K05085] [EC:2.7.10.1]
20416  
Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279]
216148  
Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447]
20418  
Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448]
271849  
Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449]
14784  
Grb2; growth factor receptor bound protein 2 [KO:K04364]
20662  
Sos1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
20663  
Sos2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
15461  
Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  
Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  
Nras; neuroblastoma ras oncogene [KO:K07828]
11836  
Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
109880  
Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
110157  
Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
26395  
Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  
Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  
Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  
Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
17869  
Myc; myelocytomatosis oncogene [KO:K04377]
14388  
Gab1; growth factor receptor bound protein 2-associated protein 1 [KO:K09593]
18183  
Nrg3; neuregulin 3 [KO:K05457]
83961  
Nrg4; neuregulin 4 [KO:K05458]
30955  
Pik3cg; phosphoinositide-3-kinase, catalytic, gamma polypeptide [KO:K00922] [EC:2.7.1.153]
18706  
Pik3ca; phosphatidylinositol 3-kinase, catalytic, alpha polypeptide [KO:K00922] [EC:2.7.1.153]
18707  
Pik3cd; phosphatidylinositol 3-kinase catalytic delta polypeptide [KO:K00922] [EC:2.7.1.153]
74769  
Pik3cb; phosphatidylinositol 3-kinase, catalytic, beta polypeptide [KO:K00922] [EC:2.7.1.153]
18709  
Pik3r2; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 2 (p85 beta) [KO:K02649]
18708  
Pik3r1; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) [KO:K02649]
320207  
Pik3r5; phosphoinositide-3-kinase, regulatory subunit 5, p101 [KO:K02649]
18710  
Pik3r3; phosphatidylinositol 3 kinase, regulatory subunit, polypeptide 3 (p55) [KO:K02649]
11651  
Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  
Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  
Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
56717  
Mtor; mechanistic target of rapamycin (serine/threonine kinase) [KO:K07203] [EC:2.7.11.1]
58988  
Rps6kb2; ribosomal protein S6 kinase, polypeptide 2 [KO:K04688] [EC:2.7.11.1]
72508  
Rps6kb1; ribosomal protein S6 kinase, polypeptide 1 [KO:K04688] [EC:2.7.11.1]
13685  
Eif4ebp1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
12015  
Bad; BCL2-associated agonist of cell death [KO:K02158]
56637  
Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
12576  
Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
12575  
Cdkn1a; cyclin-dependent kinase inhibitor 1A (P21) [KO:K06625]
Compound
C00076  
Calcium cation
C00165  
Diacylglycerol
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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
  Authors
Yarden Y, Sliwkowski MX.
  Title
Untangling the ErbB signalling network.
  Journal
Nat Rev Mol Cell Biol 2:127-37 (2001)
Reference
  Authors
Citri A, Yarden Y.
  Title
EGF-ERBB signalling: towards the systems level.
  Journal
Nat Rev Mol Cell Biol 7:505-16 (2006)
Reference
  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
  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
  Authors
Holbro T, Hynes NE.
  Title
ErbB receptors: directing key signaling networks throughout life.
  Journal
Annu Rev Pharmacol Toxicol 44:195-217 (2004)
Reference
  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
  Authors
Hynes NE, Lane HA.
  Title
ERBB receptors and cancer: the complexity of targeted inhibitors.
  Journal
Nat Rev Cancer 5:341-54 (2005)
Reference
  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
  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
  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
  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
  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
 

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