KEGG   PATHWAY: cimi04012
Entry
cimi04012                   Pathway                                
Name
ErbB signaling pathway - Cebus imitator (Panamanian white-faced capuchin)
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
cimi04012  ErbB signaling pathway
cimi04012

Organism
Cebus imitator (Panamanian white-faced capuchin) [GN:cimi]
Gene
108290027  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
108299641  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
108292190  AREG; amphiregulin [KO:K09782]
108294535  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
108281617  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
108291487  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
108313460  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
108318509  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
108290441  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
108313439  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
108293811  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
108306397  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
108281637  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
108308532  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
108282129  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
108300640  CBL; E3 ubiquitin-protein ligase CBL isoform X2 [KO:K04707] [EC:2.3.2.27]
108305841  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
108289825  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
108289827  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
108291826  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
108284810  PTK2; focal adhesion kinase 1 isoform X11 [KO:K05725] [EC:2.7.10.2]
108313339  CRK; adapter molecule crk isoform X1 [KO:K04438]
108296215  CRKL; crk-like protein [KO:K04438]
108282994  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
108301298  ABL2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
108306493  LOW QUALITY PROTEIN: cytoplasmic protein NCK1-like [KO:K07365]
108304199  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
108312933  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
108307420  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
108300154  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
108285158  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
108287866  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
108300962  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
108306138  serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
108306463  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
108283651  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
108315696  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108286678  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108295228  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
108314896  JUN; transcription factor AP-1 [KO:K04448]
108295535  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
108293447  BTC; probetacellulin isoform X1 [KO:K09783]
108310085  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
108292191  EREG; proepiregulin [KO:K09784]
108309759  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
108308927  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X2 [KO:K05455]
108310076  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
108308938  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
108292463  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
108297501  SHC2; SHC-transforming protein 2 [KO:K17447]
108304324  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
108315604  SHC4; SHC-transforming protein 4 [KO:K17449]
108309416  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
108287976  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
108293763  SOS1; son of sevenless homolog 1 [KO:K03099]
108288791  HRAS; GTPase HRas isoform X1 [KO:K02833]
108300272  KRAS; GTPase KRas isoform X2 [KO:K07827]
108289201  GTPase NRas-like [KO:K07828]
108301162  NRAS; GTPase NRas isoform X2 [KO:K07828]
108295532  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
108283419  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
108284634  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
108282680  dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
108288453  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
108296669  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108296197  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108283896  MYC; myc proto-oncogene protein [KO:K04377]
108308590  GAB1; GRB2-associated-binding protein 1 isoform X2 [KO:K09593]
108286864  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
108295885  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
108287732  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108300786  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108286022  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108312772  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
108284538  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108295514  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
108285792  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108306856  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108287186  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108285700  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
108310354  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
108312078  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
108309889  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
108310302  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
108292532  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
108304025  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
108299987  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
cimi04010  MAPK signaling pathway
cimi04020  Calcium signaling pathway
cimi04110  Cell cycle
cimi04150  mTOR signaling pathway
cimi04151  PI3K-Akt signaling pathway
cimi05212  Pancreatic cancer
cimi05213  Endometrial cancer
cimi05214  Glioma
cimi05223  Non-small cell lung cancer
KO pathway
ko04012   
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