KEGG   PATHWAY: phas04012
Entry
phas04012                   Pathway                                
Name
ErbB signaling pathway - Phyllostomus hastatus (greater spear-nosed bat)
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
phas04012  ErbB signaling pathway
phas04012

Organism
Phyllostomus hastatus (greater spear-nosed bat) [GN:phas]
Gene
123804414  NRAS; GTPase NRas [KO:K07828]
123804815  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
123805160  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
123805534  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
123805718  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
123805855  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
123806400  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
123806569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123806596  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
123806597  CRKL; crk-like protein isoform X1 [KO:K04438]
123806865  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
123806902  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123807193  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123807317  HRAS; GTPase HRas isoform X1 [KO:K02833]
123807542  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
123807573  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
123807983  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
123808110  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
123808510  [KO:K05735] [EC:2.7.11.1]
123808608  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123808639  SHC4; SHC-transforming protein 4 [KO:K17449]
123809359  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
123811120  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123811124  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
123811379  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
123811711  NCK2; cytoplasmic protein NCK2 [KO:K19862]
123811931  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
123812406  KRAS; GTPase KRas isoform X1 [KO:K07827]
123812915  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
123812935  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
123813640  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123813723  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
123813767  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
123813838  SHC2; SHC-transforming protein 2 [KO:K17447]
123814364  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123814793  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
123814829  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
123815356  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
123815569  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
123816875  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
123816974  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
123817091  [KO:K11223]
123817321  CRK; adapter molecule crk isoform X1 [KO:K04438]
123817350  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123817558  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
123817599  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
123818357  ABL2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
123818694  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
123820887  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123820930  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
123821027  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
123822234  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
123823364  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
123823743  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123823859  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
123824140  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
123824527  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123825494  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
123825523  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123825630  [KO:K04409] [EC:2.7.11.1]
123826609  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
123826750  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123826853  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
123827009  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
123827255  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
123828079  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
123828291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123829298  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
123829336  BAD; bcl2-associated agonist of cell death [KO:K02158]
123829653  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
123830555  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
123830565  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123831163  BTC; probetacellulin isoform X1 [KO:K09783]
123831167  EREG; proepiregulin [KO:K09784]
123831258  AREG; amphiregulin [KO:K09782]
123831409  JUN; transcription factor AP-1 [KO:K04448]
123831556  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
123831922  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123832297  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123832298  [KO:K02649]
123832643  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
123832645  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
123833261  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
123833339  MYC; myc proto-oncogene protein [KO:K04377]
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
phas04010  MAPK signaling pathway
phas04020  Calcium signaling pathway
phas04110  Cell cycle
phas04150  mTOR signaling pathway
phas04151  PI3K-Akt signaling pathway
phas05212  Pancreatic cancer
phas05213  Endometrial cancer
phas05214  Glioma
phas05223  Non-small cell lung cancer
KO pathway
ko04012   

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