KEGG   PATHWAY: ggo04012
Entry
ggo04012                    Pathway                                
Name
ErbB signaling pathway - Gorilla gorilla gorilla (western lowland gorilla)
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
ggo04012  ErbB signaling pathway
ggo04012

Organism
Gorilla gorilla gorilla (western lowland gorilla) [GN:ggo]
Gene
101153700  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
101140326  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
101139901  AREG; amphiregulin [KO:K09782]
101126190  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
101140885  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X2 [KO:K05083] [EC:2.7.10.1]
101135199  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101133643  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101134676  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X29 [KO:K04515] [EC:2.7.11.17]
101153594  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101148194  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101136547  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101124828  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101150691  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101139074  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101140325  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
101124684  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
101134686  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
101128930  signal transducer and activator of transcription 5B isoform X2 [KO:K11224]
101153251  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
101128620  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
101127403  CRKL; crk-like protein [KO:K04438]
101127165  ABL1; tyrosine-protein kinase ABL1 isoform X2 [KO:K06619] [EC:2.7.10.2]
101134626  ABL2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
101140243  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
101150520  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
101138276  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
101130725  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
101141425  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
101127864  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
101124352  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
101140999  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
101154090  dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
101143954  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
101124339  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X4 [KO:K04431] [EC:2.7.12.2]
101152026  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101124033  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
101133141  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101145729  JUN; transcription factor AP-1 [KO:K04448]
101133308  ELK1; LOW QUALITY PROTEIN: ETS domain-containing protein Elk-1 [KO:K04375]
101140250  BTC; probetacellulin isoform X1 [KO:K09783]
101138938  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
101136229  EREG; proepiregulin [KO:K09784]
109025126  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
101132579  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
101152152  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
101131773  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
101136424  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
101129046  SHC2; SHC-transforming protein 2 [KO:K17447]
101127418  SHC3; SHC-transforming protein 3 isoform X2 [KO:K17448]
101154420  SHC4; SHC-transforming protein 4 [KO:K17449]
101133976  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101130824  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101137539  SOS2; son of sevenless homolog 2 [KO:K03099]
101136425  HRAS; GTPase HRas isoform X1 [KO:K02833]
101144039  KRAS; GTPase KRas isoform X1 [KO:K07827]
101146562  NRAS; GTPase NRas [KO:K07828]
101134493  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101145098  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
101136454  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:2.7.11.1]
101132391  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101126885  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101140164  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101135988  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101137026  MYC; myc proto-oncogene protein [KO:K04377]
101147447  GAB1; GRB2-associated-binding protein 1 isoform X2 [KO:K09593]
101124641  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X3 [KO:K05457]
101154061  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
101143811  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101146434  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101152123  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101130978  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
101135298  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101129336  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101137723  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101138019  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101138990  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101134525  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
101126746  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101145454  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101151128  BAD; bcl2-associated agonist of cell death [KO:K02158]
101125534  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101147653  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101126640  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
ggo04010  MAPK signaling pathway
ggo04020  Calcium signaling pathway
ggo04110  Cell cycle
ggo04150  mTOR signaling pathway
ggo04151  PI3K-Akt signaling pathway
ggo05212  Pancreatic cancer
ggo05213  Endometrial cancer
ggo05214  Glioma
ggo05223  Non-small cell lung cancer
KO pathway
ko04012   
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