KEGG   PATHWAY: panu04012
Entry
panu04012                   Pathway                                
Name
ErbB signaling pathway - Papio anubis (olive baboon)
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
panu04012  ErbB signaling pathway
panu04012

Organism
Papio anubis (olive baboon) [GN:panu]
Gene
100137333  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100381179  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100510873  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X4 [KO:K02649]
100997634  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100998364  [KO:K11223]
100998445  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
100998800  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100998866  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100999911  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101000002  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
101000402  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101000409  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
101000645  MYC; myc proto-oncogene protein [KO:K04377]
101001301  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X2 [KO:K05456]
101001461  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101001939  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
101001946  ABL2; tyrosine-protein kinase ABL2 isoform X10 [KO:K08887] [EC:2.7.10.2]
101002278  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101002457  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
101002675  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101002971  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101002992  HRAS; GTPase HRas isoform X2 [KO:K02833]
101003160  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
101003588  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
101003749  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101003778  ERBB3; receptor tyrosine-protein kinase erbB-3 isoform X1 [KO:K05084] [EC:2.7.10.1]
101004074  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101004091  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
101004976  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101005010  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
101005565  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
101005723  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
101006054  [KO:K17447]
101006756  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101007122  CRKL; crk-like protein [KO:K04438]
101007278  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
101007628  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
101008394  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101008699  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101008734  GAB1; GRB2-associated-binding protein 1 isoform X4 [KO:K09593]
101008748  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
101008925  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X10 [KO:K04515] [EC:2.7.11.17]
101009029  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101009865  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101009981  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101009984  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X37 [KO:K04515] [EC:2.7.11.17]
101010894  JUN; transcription factor AP-1 [KO:K04448]
101011087  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101011142  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
101011160  CRK; adapter molecule crk isoform X1 [KO:K04438]
101011807  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101012038  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
101012041  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101012071  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
101012165  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
101012551  BAD; bcl2-associated agonist of cell death [KO:K02158]
101013880  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
101014651  [KO:K17449]
101015041  MTOR; serine/threonine-protein kinase mTOR isoform X2 [KO:K07203] [EC:2.7.11.1]
101015667  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X2 [KO:K04430] [EC:2.7.12.2]
101016376  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
101016445  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X4 [KO:K05455]
101016532  PRKCA; protein kinase C alpha type isoform X4 [KO:K02677] [EC:2.7.11.13]
101016679  NRG4; pro-neuregulin-4, membrane-bound isoform isoform X1 [KO:K05458]
101016859  NCK2; cytoplasmic protein NCK2 isoform X2 [KO:K19862]
101017528  KRAS; GTPase KRas isoform X2 [KO:K07827]
101019640  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101019884  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101019885  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X18 [KO:K04515] [EC:2.7.11.17]
101020518  PAK2; serine/threonine-protein kinase PAK 2 isoform X1 [KO:K04410] [EC:2.7.11.1]
101020682  BTC; probetacellulin isoform X1 [KO:K09783]
101021018  AREG; amphiregulin isoform X1 [KO:K09782]
101021732  EREG; proepiregulin [KO:K09784]
101021974  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
101022024  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101022320  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101022780  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
101022936  PTK2; focal adhesion kinase 1 isoform X25 [KO:K05725] [EC:2.7.10.2]
101023802  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
101024393  SHC3; SHC-transforming protein 3 [KO:K17448]
101024761  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101025530  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101026253  NRAS; GTPase NRas isoform X2 [KO:K07828]
101026665  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
116269450  [KO:K04515] [EC:2.7.11.17]
116269451  [KO:K04515] [EC:2.7.11.17]
116272720  [KO:K17449]
116272724  [KO:K17449]
116272729  [KO:K17449]
116272733  [KO:K17449]
116272789  [KO:K17449]
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
panu04010  MAPK signaling pathway
panu04020  Calcium signaling pathway
panu04110  Cell cycle
panu04150  mTOR signaling pathway
panu04151  PI3K-Akt signaling pathway
panu05212  Pancreatic cancer
panu05213  Endometrial cancer
panu05214  Glioma
panu05223  Non-small cell lung cancer
KO pathway
ko04012   

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