KEGG   PATHWAY: chx04012
Entry
chx04012                    Pathway                                
Name
ErbB signaling pathway - Capra hircus (goat)
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
chx04012  ErbB signaling pathway
chx04012

Organism
Capra hircus (goat) [GN:chx]
Gene
100860902  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100860904  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100860973  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
100861087  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100861234  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100861297  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
102168328  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
102168391  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102169319  [KO:K04688] [EC:2.7.11.1]
102169370  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
102169956  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
102170129  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
102170135  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102170356  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102170408  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102170926  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
102171262  MYC; myc proto-oncogene protein [KO:K04377]
102172114  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
102172519  KRAS; GTPase KRas isoform X1 [KO:K07827]
102172767  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102173178  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102173448  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
102174051  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102174330  CRK; adapter molecule crk isoform X1 [KO:K04438]
102174360  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
102175206  CRKL; crk-like protein [KO:K04438]
102175277  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102175285  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102175799  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
102175934  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
102175984  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102176363  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102176415  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
102176762  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
102176919  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
102177551  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102177814  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
102179343  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102179773  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
102179898  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102179970  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
102180167  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
102180337  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
102180601  NCK2; cytoplasmic protein NCK2 [KO:K19862]
102180661  AREG; amphiregulin isoform X3 [KO:K09782]
102180827  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102180890  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102181217  PAK5; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
102181878  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102181989  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
102182530  PAK4; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
102182565  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
102182675  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
102182774  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102182890  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102183226  EREG; proepiregulin isoform X1 [KO:K09784]
102183402  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
102183499  BTC; probetacellulin [KO:K09783]
102184154  SOS2; son of sevenless homolog 2 [KO:K03099]
102184349  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
102184950  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
102185042  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102185084  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102185177  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
102185385  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
102185423  JUN; transcription factor AP-1 [KO:K04448]
102185462  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
102185660  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102185715  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
102185866  [KO:K11223]
102185926  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
102186040  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102186140  ABL2; Abelson tyrosine-protein kinase 2 isoform X3 [KO:K08887] [EC:2.7.10.2]
102186668  HRAS; GTPase HRas isoform X1 [KO:K02833]
102186998  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102187180  NRAS; GTPase NRas [KO:K07828]
102187521  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102188710  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102188824  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102189677  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
102189930  BAD; bcl2-associated agonist of cell death [KO:K02158]
102189995  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
102190520  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X4 [KO:K04368] [EC:2.7.12.2]
106502173  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
108638619  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
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
chx04010  MAPK signaling pathway
chx04020  Calcium signaling pathway
chx04110  Cell cycle
chx04150  mTOR signaling pathway
chx04151  PI3K-Akt signaling pathway
chx05212  Pancreatic cancer
chx05213  Endometrial cancer
chx05214  Glioma
chx05223  Non-small cell lung cancer
KO pathway
ko04012   

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