KEGG   PATHWAY: ray04012
Entry
ray04012                    Pathway                                

Name
ErbB signaling pathway - Rousettus aegyptiacus (Egyptian rousette)
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
ray04012  ErbB signaling pathway
ray04012

Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107508819  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
107519111  TGFA; protransforming growth factor alpha [KO:K08774]
107515312  AREG; LOW QUALITY PROTEIN: amphiregulin [KO:K09782]
107498193  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
107520699  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
107506741  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
107521319  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
107510894  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
107512385  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
107497167  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
107498266  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
107510307  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
107516091  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
107503061  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
107507930  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
107514119  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
107513821  signal transducer and activator of transcription 5A [KO:K11223]
107513822  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
107512598  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
107504408  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
107507729  CRK; adapter molecule crk isoform X1 [KO:K04438]
107497859  CRKL; crk-like protein [KO:K04438]
107504550  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
107509025  ABL2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:2.7.10.2]
107513946  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
107509617  NCK2; cytoplasmic protein NCK2 [KO:K19862]
107519160  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
107505275  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
107502306  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
107520962  PAK4; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
107497004  PAK7; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
107514462  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
107517401  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
107519926  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
107512328  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107509910  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107515392  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107518352  JUN; transcription factor AP-1 [KO:K04448]
107509357  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
107515327  BTC; probetacellulin [KO:K09783]
107521572  HBEGF; LOW QUALITY PROTEIN: proheparin-binding EGF-like growth factor [KO:K08523]
107515330  EREG; proepiregulin [KO:K09784]
107521255  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
107505812  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
107521551  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
107517636  ERBB4; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
107505474  SHC1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
107512423  LOW QUALITY PROTEIN: SHC-transforming protein 1-like [KO:K06279]
107500961  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
107504308  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
107519965  SHC4; SHC-transforming protein 4 [KO:K17449]
107503781  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
107519446  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107511436  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
107507127  HRAS; GTPase HRas isoform X1 [KO:K02833]
107497434  KRAS; GTPase KRas isoform X1 [KO:K07827]
107499847  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
107509353  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
107504052  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
107519729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
107508942  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
107510634  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107506202  MYC; myc proto-oncogene protein [KO:K04377]
107499274  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
107498386  NRG3; LOW QUALITY PROTEIN: pro-neuregulin-3, membrane-bound isoform [KO:K05457]
107520152  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107517828  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107513958  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107521668  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
107517899  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
107498704  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107513978  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107521783  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107498395  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107513109  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
107503682  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
107510136  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
107515968  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
107497091  BAD; bcl2-associated agonist of cell death [KO:K02158]
107517741  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107516566  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
107514682  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [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
ray04010  MAPK signaling pathway
ray04020  Calcium signaling pathway
ray04110  Cell cycle
ray04150  mTOR signaling pathway
ray04151  PI3K-Akt signaling pathway
ray05212  Pancreatic cancer
ray05213  Endometrial cancer
ray05214  Glioma
ray05223  Non-small cell lung cancer
KO pathway
ko04012   
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