KEGG   PATHWAY: ccad04012
Entry
ccad04012                   Pathway                                
Name
ErbB signaling pathway - Cervus canadensis (wapiti)
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
ccad04012  ErbB signaling pathway
ccad04012

Organism
Cervus canadensis (wapiti) [GN:ccad]
Gene
122422171  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
122441530  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
122428214  AREG; amphiregulin [KO:K09782]
122424243  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
122448704  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
122420118  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
122438529  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
122439705  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
122422042  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
122446388  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
122424748  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
122433081  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
122420171  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
122450328  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
122428853  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
122441616  signal transducer and activator of transcription 5A [KO:K11223]
122441627  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
122448145  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
122451056  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
122447839  CRK; adapter molecule crk isoform X1 [KO:K04438]
122455174  CRKL; crk-like protein [KO:K04438]
122442277  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
122451809  ABL2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
122445291  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
122441792  NCK2; cytoplasmic protein NCK2 [KO:K19862]
122430687  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
122444682  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
122434452  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
122420521  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
122448747  PAK5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
122443381  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
122445001  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
122428005  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
122440347  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
122440572  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
122428339  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
122446321  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122436906  JUN; transcription factor AP-1 [KO:K04448]
122434868  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
122428331  BTC; probetacellulin isoform X1 [KO:K09783]
122439834  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
122428017  EREG; proepiregulin [KO:K09784]
122427060  ERBB3; receptor tyrosine-protein kinase ErbB-3 [KO:K05084] [EC:2.7.10.1]
122432432  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
122439835  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
122426466  ERBB4; receptor tyrosine-protein kinase ErbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
122432839  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
122431762  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
122443633  SHC4; SHC-transforming protein 4 [KO:K17449]
122436698  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
122441591  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
122443464  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
122430591  HRAS; GTPase HRas isoform X1 [KO:K02833]
122423876  KRAS; GTPase KRas isoform X1 [KO:K07827]
122446047  GTPase KRas [KO:K07827]
122435924  NRAS; GTPase NRas [KO:K07828]
122434589  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
122438725  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
122425059  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122443062  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122440231  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
122440910  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
122446062  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
122447261  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
122433033  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122455309  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122451212  MYC; myc proto-oncogene protein [KO:K04377]
122452084  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
122446443  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
122455121  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
122451688  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122445271  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122444906  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122440740  PIK3R2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122454626  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122437038  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
122420500  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122452448  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122455107  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122452383  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
122430962  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
122450141  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
122432485  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
122430652  BAD; bcl2-associated agonist of cell death [KO:K02158]
122445589  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
122423697  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
122429747  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
ccad04010  MAPK signaling pathway
ccad04020  Calcium signaling pathway
ccad04110  Cell cycle
ccad04150  mTOR signaling pathway
ccad04151  PI3K-Akt signaling pathway
ccad05212  Pancreatic cancer
ccad05213  Endometrial cancer
ccad05214  Glioma
ccad05223  Non-small cell lung cancer
KO pathway
ko04012   
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