KEGG   PATHWAY: aamp04012
Entry
aamp04012                   Pathway                                
Name
ErbB signaling pathway - Arvicola amphibius (Eurasian water vole)
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
aamp04012  ErbB signaling pathway
aamp04012

Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119800249  Hras; GTPase HRas isoform X1 [KO:K02833]
119800462  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
119800744  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
119800784  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
119800992  Egf; pro-epidermal growth factor [KO:K04357]
119801497  Nras; GTPase NRas [KO:K07828]
119801740  Btc; probetacellulin [KO:K09783]
119801830  Gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
119801950  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
119802636  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
119803504  Erbb3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
119804230  [KO:K07827]
119804537  Elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
119804765  Pak3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
119805132  Araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
119805902  [KO:K04366] [EC:2.7.11.1]
119806318  Kras; GTPase KRas isoform X1 [KO:K07827]
119806329  Sos1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
119806667  Braf; LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
119807071  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
119807169  Tgfa; protransforming growth factor alpha [KO:K08774]
119808272  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
119808786  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
119808979  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119809093  Nrg4; pro-neuregulin-4, membrane-bound isoform isoform X1 [KO:K05458]
119809631  Cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
119809695  Nck1; cytoplasmic protein NCK1 [KO:K07365]
119809903  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119810503  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119811038  [KO:K11224]
119811270  Mapk9; LOW QUALITY PROTEIN: mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
119811714  Nrg1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
119811725  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
119811835  Crk; adapter molecule crk isoform X1 [KO:K04438]
119812102  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119812127  [KO:K11223]
119812144  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
119812357  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
119813014  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
119813036  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
119813254  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
119813356  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119813574  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
119813700  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
119814097  Areg; amphiregulin [KO:K09782]
119814207  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
119814221  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
119814345  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
119814664  [KO:K05735] [EC:2.7.11.1]
119814876  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
119814969  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
119814980  Nrg2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
119815102  Pak5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
119815646  Shc4; SHC-transforming protein 4 isoform X1 [KO:K17449]
119816315  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119816408  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
119816694  Jun; transcription factor AP-1 [KO:K04448]
119817129  Shc3; SHC-transforming protein 3 [KO:K17448]
119817743  [KO:K02649]
119818434  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
119818643  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119818860  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
119820487  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119820525  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
119820784  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
119821511  Pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
119821978  Erbb4; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
119822917  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
119822940  Myc; myc proto-oncogene protein [KO:K04377]
119823049  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
119823603  Nck2; cytoplasmic protein NCK2 [KO:K19862]
119823930  Ptk2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
119824224  Gsk3b; LOW QUALITY PROTEIN: glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
119824571  Cblb; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
119824680  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119824768  Crkl; crk-like protein [KO:K04438]
119824822  Pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
119824883  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
119825434  Shc2; SHC-transforming protein 2 [KO:K17447]
119826317  Pik3ca; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119827095  Nrg3; pro-neuregulin-3, membrane-bound isoform [KO:K05457]
119827246  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
119827427  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
119827491  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
119827876  Abl2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
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)
DOI:10.1016/j.ijrobp.2003.06.002
Reference
  Authors
Yarden Y, Sliwkowski MX.
  Title
Untangling the ErbB signalling network.
  Journal
Nat Rev Mol Cell Biol 2:127-37 (2001)
DOI:10.1038/35052073
Reference
  Authors
Citri A, Yarden Y.
  Title
EGF-ERBB signalling: towards the systems level.
  Journal
Nat Rev Mol Cell Biol 7:505-16 (2006)
DOI:10.1038/nrm1962
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)
DOI:10.1158/1078-0432.CCR-05-1554
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)
DOI:10.1016/j.gene.2005.10.018
Reference
  Authors
Holbro T, Hynes NE.
  Title
ErbB receptors: directing key signaling networks throughout life.
  Journal
Annu Rev Pharmacol Toxicol 44:195-217 (2004)
DOI:10.1146/annurev.pharmtox.44.101802.121440
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)
DOI:10.4161/cc.2.4.433
Reference
  Authors
Hynes NE, Lane HA.
  Title
ERBB receptors and cancer: the complexity of targeted inhibitors.
  Journal
Nat Rev Cancer 5:341-54 (2005)
DOI:10.1038/nrc1609
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)
DOI:10.1038/msb4100014
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)
DOI:10.1038/msb4100012
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)
DOI:10.1093/emboj/19.13.3159
Reference
PMID:9872057
  Authors
McCarty JH.
  Title
The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.
  Journal
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)
DOI:10.1074/jbc.M414044200
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)
DOI:10.1128/MCB.19.10.6845
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)
DOI:10.1074/jbc.273.27.17186
Related
pathway
aamp04010  MAPK signaling pathway
aamp04020  Calcium signaling pathway
aamp04110  Cell cycle
aamp04150  mTOR signaling pathway
aamp04151  PI3K-Akt signaling pathway
aamp05212  Pancreatic cancer
aamp05213  Endometrial cancer
aamp05214  Glioma
aamp05223  Non-small cell lung cancer
KO pathway
ko04012   

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