KEGG   PATHWAY: rro04012
Entry
rro04012                    Pathway                                

Name
ErbB signaling pathway - Rhinopithecus roxellana (golden snub-nosed monkey)
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
rro04012  ErbB signaling pathway
rro04012

Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104682421  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
104661322  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
104673173  AREG; amphiregulin [KO:K09782]
104675886  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
104674848  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
104672220  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
104671624  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
104676623  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
104670410  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
104671146  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
104669984  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
104675428  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
104665907  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
104676027  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
104657236  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
104674409  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
104680310  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
104680321  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
104655840  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
115895854  proto-oncogene tyrosine-protein kinase Src-like [KO:K05704] [EC:2.7.10.2]
104679749  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
104666852  CRKL; crk-like protein [KO:K04438]
104670311  CRK; adapter molecule crk isoform X1 [KO:K04438]
104660552  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
104672008  ABL2; tyrosine-protein kinase ABL2 isoform X4 [KO:K08887] [EC:2.7.10.2]
104663559  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
104660581  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
104664316  PAK1; serine/threonine-protein kinase PAK 1 isoform X5 [KO:K04409] [EC:2.7.11.1]
104676374  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
104668306  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
104676163  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
104655775  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
104659671  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
104672345  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X2 [KO:K04430] [EC:2.7.12.2]
104679497  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
104676194  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104678447  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104668007  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104664278  JUN; transcription factor AP-1 [KO:K04448]
104664595  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
104673171  BTC; probetacellulin [KO:K09783]
104681756  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
104673174  EREG; proepiregulin [KO:K09784]
104673694  ERBB3; receptor tyrosine-protein kinase erbB-3 isoform X1 [KO:K05084] [EC:2.7.10.1]
104668214  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X5 [KO:K05455]
104681858  NRG2; pro-neuregulin-2, membrane-bound isoform [KO:K05456]
104658903  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
104663483  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
104668515  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
104657941  SHC4; SHC-transforming protein 4 [KO:K17449]
104681311  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
104663024  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
104682751  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
104654600  HRAS; GTPase HRas isoform X1 [KO:K02833]
104670041  KRAS; GTPase KRas isoform X1 [KO:K07827]
104669078  NRAS; GTPase NRas [KO:K07828]
104664593  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
104659700  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
104673299  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
104662575  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104665487  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104676897  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104681150  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104674798  MYC; myc proto-oncogene protein [KO:K04377]
104657016  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
104672529  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
104672054  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
104663050  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104665061  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104670605  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104662124  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104675620  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104680672  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104673041  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104676121  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104654186  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
115893905  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104654362  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
104662932  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
104664740  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
104679650  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
104673141  BAD; bcl2-associated agonist of cell death [KO:K02158]
104680990  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
104668343  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
104682880  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
rro04010  MAPK signaling pathway
rro04020  Calcium signaling pathway
rro04110  Cell cycle
rro04150  mTOR signaling pathway
rro04151  PI3K-Akt signaling pathway
rro05212  Pancreatic cancer
rro05213  Endometrial cancer
rro05214  Glioma
rro05223  Non-small cell lung cancer
KO pathway
ko04012   
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