KEGG   PATHWAY: cfr04012
Entry
cfr04012                    Pathway                                
Name
ErbB signaling pathway - Camelus ferus (Wild Bactrian camel)
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
cfr04012  ErbB signaling pathway
cfr04012

Organism
Camelus ferus (Wild Bactrian camel) [GN:cfr]
Gene
102523769  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102506694  TGFA; protransforming growth factor alpha [KO:K08774]
102507976  AREG; amphiregulin [KO:K09782]
102504272  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102519604  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
102524452  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102514470  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
102522167  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
102512557  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102521522  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
102506589  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
102507832  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
102511859  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
102513516  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102504124  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
102515465  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102520794  signal transducer and activator of transcription 5A [KO:K11223]
102511001  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
102520048  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102516584  CRKL; crk-like protein [KO:K04438]
102511476  CRK; adapter molecule crk isoform X1 [KO:K04438]
102519310  ABL1; tyrosine-protein kinase ABL1 isoform X2 [KO:K06619] [EC:2.7.10.2]
102517204  ABL2; tyrosine-protein kinase ABL2 isoform X5 [KO:K08887] [EC:2.7.10.2]
102516504  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
102509285  NCK2; cytoplasmic protein NCK2 [KO:K19862]
102514942  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102504877  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
102517603  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
102522034  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
102512936  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
102521615  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
102513578  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
102506459  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102518561  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102509448  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102503577  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102516943  JUN; transcription factor AP-1 [KO:K04448]
102507567  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
102508543  BTC; probetacellulin [KO:K09783]
102510168  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
102507712  EREG; proepiregulin [KO:K09784]
102506629  ERBB3; receptor tyrosine-protein kinase erbB-3 isoform X1 [KO:K05084] [EC:2.7.10.1]
102510288  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X5 [KO:K05455]
102510636  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
102522654  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
102524489  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
102506382  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
102508169  SHC3; SHC-transforming protein 3 [KO:K17448]
102517753  SHC4; SHC-transforming protein 4 [KO:K17449]
102515306  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102507247  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102517014  SOS2; son of sevenless homolog 2 [KO:K03099]
102524334  HRAS; GTPase HRas isoform X1 [KO:K02833]
102516372  KRAS; GTPase KRas isoform X1 [KO:K07827]
102509562  NRAS; GTPase NRas [KO:K07828]
102506774  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
102524100  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
102517521  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102515937  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102511209  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102517586  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102521659  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102511086  MYC; myc proto-oncogene protein [KO:K04377]
102512457  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
102514418  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
102522168  NRG4; pro-neuregulin-4, membrane-bound isoform isoform X1 [KO:K05458]
102523502  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102518643  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102519994  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102513205  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102505690  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102520923  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102503460  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102515350  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102519101  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
106729149  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102510836  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
102518322  RPS6KB2; LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
102511731  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
102520195  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
102523295  BAD; bcl2-associated agonist of cell death isoform X2 [KO:K02158]
102504696  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102518884  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102509404  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [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
cfr04010  MAPK signaling pathway
cfr04020  Calcium signaling pathway
cfr04110  Cell cycle
cfr04150  mTOR signaling pathway
cfr04151  PI3K-Akt signaling pathway
cfr05212  Pancreatic cancer
cfr05213  Endometrial cancer
cfr05214  Glioma
cfr05223  Non-small cell lung cancer
KO pathway
ko04012   
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