KEGG   PATHWAY: bom04012
Entry
bom04012                    Pathway                                
Name
ErbB signaling pathway - Bos mutus (wild yak)
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
bom04012  ErbB signaling pathway
bom04012

Organism
Bos mutus (wild yak) [GN:bom]
Gene
102264981  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
102265099  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102265427  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102265581  NRG4; pro-neuregulin-4, membrane-bound isoform isoform X1 [KO:K05458]
102265783  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
102265814  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
102265831  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102266298  ABL2; LOW QUALITY PROTEIN: tyrosine-protein kinase ABL2 [KO:K08887] [EC:2.7.10.2]
102266301  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
102266922  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102266960  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102267895  JUN; transcription factor Jun [KO:K04448]
102267975  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
102268672  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102268950  SHC3; SHC-transforming protein 3 [KO:K17448]
102269203  NRAS; GTPase NRas [KO:K07828]
102269333  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
102269655  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
102269868  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
102270841  AREG; amphiregulin [KO:K09782]
102271079  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
102271128  BTC; probetacellulin isoform X1 [KO:K09783]
102271451  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
102271710  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X2 [KO:K04369] [EC:2.7.12.2]
102272368  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102272421  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102272535  EREG; proepiregulin isoform X1 [KO:K09784]
102272638  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102273820  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
102274116  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
102274304  MYC; LOW QUALITY PROTEIN: myc proto-oncogene protein [KO:K04377]
102274461  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102274553  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102274792  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
102275091  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
102275260  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102275975  BAD; bcl2-associated agonist of cell death [KO:K02158]
102276245  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102277011  HRAS; GTPase HRas isoform X1 [KO:K02833]
102277025  CRKL; crk-like protein [KO:K04438]
102277040  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
102277548  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102277585  SOS2; son of sevenless homolog 2 [KO:K03099]
102277976  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102278368  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
102278591  [KO:K02833]
102278631  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
102278724  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
102278844  CRK; adapter molecule crk isoform X1 [KO:K04438]
102279176  CBL; E3 ubiquitin-protein ligase CBL isoform X2 [KO:K04707] [EC:2.3.2.27]
102279381  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
102279565  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
102279803  NCK1; SH2/SH3 adapter protein NCK1 isoform X1 [KO:K07365]
102279804  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
102280002  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
102280095  PTK2; LOW QUALITY PROTEIN: focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
102280296  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
102280670  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102281047  SHC2; SHC-transforming protein 2 [KO:K17447]
102281727  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
102281822  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
102282641  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
102282859  GAB1; GRB2-associated-binding protein 1 isoform X2 [KO:K09593]
102282927  [KO:K11223]
102283032  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
102283211  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
102283212  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102284488  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
102284506  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
102284931  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102285079  ARAF; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
102285300  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
102285596  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102285710  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
102285914  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
102286114  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
102286241  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102286500  KRAS; GTPase KRas isoform X1 [KO:K07827]
102286868  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102286943  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102287221  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102287278  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
102288216  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102288324  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
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
bom04010  MAPK signaling pathway
bom04020  Calcium signaling pathway
bom04110  Cell cycle
bom04150  mTOR signaling pathway
bom04151  PI3K-Akt signaling pathway
bom05212  Pancreatic cancer
bom05213  Endometrial cancer
bom05214  Glioma
bom05223  Non-small cell lung cancer
KO pathway
ko04012   

DBGET integrated database retrieval system