KEGG   PATHWAY: pon04012
Entry
pon04012                    Pathway                                

Name
ErbB signaling pathway - Pongo abelii (Sumatran orangutan)
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
pon04012  ErbB signaling pathway
pon04012

Organism
Pongo abelii (Sumatran orangutan) [GN:pon]
Gene
100455021  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
100172994  TGFA; protransforming growth factor alpha precursor [KO:K08774]
100443606  AREG; amphiregulin [KO:K09782]
100459280  EGFR; epidermal growth factor receptor isoform X2 [KO:K04361] [EC:2.7.10.1]
100450307  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
100450941  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
100457650  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
100433531  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
100172212  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
100462386  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100436747  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
100434355  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100439900  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100451563  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100462634  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
100452289  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
100461695  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
100462537  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
100436498  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
100447959  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
100452410  CRK; adapter molecule crk isoform X1 [KO:K04438]
100443298  CRKL; crk-like protein [KO:K04438]
100453216  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100437449  ABL2; Abelson tyrosine-protein kinase 2 isoform X2 [KO:K08887] [EC:2.7.10.2]
100171550  NCK1; cytoplasmic protein NCK1 [KO:K07365]
100452789  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
100449316  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
100439815  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
100294571  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
100457556  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
100174593  PAK7; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
100172971  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
100439299  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
100431600  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X2 [KO:K04431] [EC:2.7.12.2]
100174482  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100459133  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100437424  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100450292  JUN; transcription factor AP-1 [KO:K04448]
100432611  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
100445807  BTC; probetacellulin isoform X1 [KO:K09783]
100437870  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
100443243  EREG; proepiregulin [KO:K09784]
100174431  ERBB3; receptor tyrosine-protein kinase erbB-3 precursor [KO:K05084] [EC:2.7.10.1]
100171905  NRG1; pro-neuregulin-1, membrane-bound isoform [KO:K05455]
100432995  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
100938677  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
100173225  SHC1; SHC-transforming protein 1 [KO:K06279]
100445042  SHC2; SHC-transforming protein 2 [KO:K17447]
100462011  SHC3; SHC-transforming protein 3 [KO:K17448]
100431574  SHC4; SHC-transforming protein 4 [KO:K17449]
100173972  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100434331  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100458733  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100459427  HRAS; GTPase HRas [KO:K02833]
100462513  KRAS; GTPase KRas isoform X1 [KO:K07827]
100174317  NRAS; GTPase NRas precursor [KO:K07828]
100431871  ARAF; serine/threonine-protein kinase A-Raf isoform X4 [KO:K08845] [EC:2.7.11.1]
100442288  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100173732  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
100446021  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100450988  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100169740  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100431824  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100456735  MYC; myc proto-oncogene protein [KO:K04377]
100458884  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
100460909  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
100446528  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
100432846  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100453779  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103889133  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100174298  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100173589  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100437617  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100454279  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100448114  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100442100  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100456786  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100462008  LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
100459428  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
100456988  RPS6KB1; LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
100455169  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100454097  BAD; bcl2-associated agonist of cell death [KO:K02158]
100447772  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100449905  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100453682  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
pon04010  MAPK signaling pathway
pon04020  Calcium signaling pathway
pon04110  Cell cycle
pon04150  mTOR signaling pathway
pon04151  PI3K-Akt signaling pathway
pon05212  Pancreatic cancer
pon05213  Endometrial cancer
pon05214  Glioma
pon05223  Non-small cell lung cancer
KO pathway
ko04012   
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