KEGG   PATHWAY: pteh04012
Entry
pteh04012                   Pathway                                
Name
ErbB signaling pathway - Piliocolobus tephrosceles (Ugandan red Colobus)
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
pteh04012  ErbB signaling pathway
pteh04012

Organism
Piliocolobus tephrosceles (Ugandan red Colobus) [GN:pteh]
Gene
111547933  EGF; pro-epidermal growth factor [KO:K04357]
111550529  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
111524578  AREG; amphiregulin [KO:K09782]
111555709  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111537465  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
111553217  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
111552578  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
111552236  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
111552636  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
111537843  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
111547908  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
111542503  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111524197  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111530493  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
111540239  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
111542832  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
111537370  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
111537374  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
111553268  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
111553372  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
111530661  CRKL; crk-like protein [KO:K04438]
111530638  CRK; adapter molecule crk isoform X1 [KO:K04438]
111545838  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
111555318  ABL2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
111523347  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
111542152  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
111540806  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
111544329  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
111536669  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
111554067  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
111546512  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
113219483  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
111523480  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
111522663  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
111530867  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111535725  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111554538  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
111523160  JUN; transcription factor AP-1 [KO:K04448]
111535736  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
111524582  BTC; probetacellulin isoform X1 [KO:K09783]
111528287  proheparin-binding EGF-like growth factor [KO:K08523]
113224858  proheparin-binding EGF-like growth factor [KO:K08523]
111524571  EREG; proepiregulin [KO:K09784]
111541863  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
111544148  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
111528367  pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
113224859  pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
111548039  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
111543732  SHC1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
111528883  SHC2; SHC-transforming protein 2 [KO:K17447]
111527961  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
111552722  SHC4; SHC-transforming protein 4 [KO:K17449]
111542428  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
111545353  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
111549528  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
111540622  KRAS; GTPase KRas isoform X1 [KO:K07827]
111549619  NRAS; GTPase NRas [KO:K07828]
111536410  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
111521522  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
111546904  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111548354  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111521954  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111530673  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111525729  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
111550563  MYC; myc proto-oncogene protein [KO:K04377]
111551919  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
111551984  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
111530419  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
111521403  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111544647  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111523340  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111554247  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111539891  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111548774  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
111554120  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111545216  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111538340  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111526309  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
111522215  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X2 [KO:K04688] [EC:2.7.11.1]
111544131  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 isoform X1 [KO:K07205]
111522294  BAD; bcl2-associated agonist of cell death [KO:K02158]
111543871  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111552085  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
111542983  CDKN1A; cyclin-dependent kinase inhibitor 1 [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)
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
pteh04010  MAPK signaling pathway
pteh04020  Calcium signaling pathway
pteh04110  Cell cycle
pteh04150  mTOR signaling pathway
pteh04151  PI3K-Akt signaling pathway
pteh05212  Pancreatic cancer
pteh05213  Endometrial cancer
pteh05214  Glioma
pteh05223  Non-small cell lung cancer
KO pathway
ko04012   
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