KEGG   PATHWAY: hai04012
Entry
hai04012                    Pathway                                
Name
ErbB signaling pathway - Hipposideros armiger (great roundleaf 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
hai04012  ErbB signaling pathway
hai04012

Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109379436  EGF; pro-epidermal growth factor [KO:K04357]
109385384  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
109371841  AREG; amphiregulin [KO:K09782]
109388365  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
109380800  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
109379925  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
109378365  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
109372542  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109373019  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109375001  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
109390284  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
109380289  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109386578  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109372505  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
109393876  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
109395019  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
109395760  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
109377191  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
109390857  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
109386906  CRK; adapter molecule crk isoform X1 [KO:K04438]
109376239  CRKL; crk-like protein [KO:K04438]
109380669  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
109384874  ABL2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:2.7.10.2]
109389242  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
109374107  NCK2; cytoplasmic protein NCK2 [KO:K19862]
109376015  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
109387639  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
109392102  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
109395380  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
109378999  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
109384074  serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
109389137  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
109396087  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
109392215  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109377948  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
109392748  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
109371251  JUN; transcription factor AP-1 [KO:K04448]
109371257  transcription factor AP-1 [KO:K04448]
109376565  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
109371840  BTC; probetacellulin [KO:K09783]
109392466  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
109371839  EREG; proepiregulin [KO:K09784]
109396911  ERBB3; receptor tyrosine-protein kinase erbB-3 isoform X1 [KO:K05084] [EC:2.7.10.1]
109382960  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
109393067  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
109390432  ERBB4; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
109393422  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
109390676  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
109376923  SHC3; SHC-transforming protein 3 [KO:K17448]
109394486  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
109383688  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
109385471  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
109375221  SOS2; son of sevenless homolog 2 [KO:K03099]
109375639  HRAS; GTPase HRas isoform X1 [KO:K02833]
109385150  GTPase HRas-like [KO:K02833]
109389264  KRAS; GTPase KRas isoform X1 [KO:K07827]
109377015  NRAS; GTPase NRas [KO:K07828]
109376563  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
109395605  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
109384548  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109385252  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109388626  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109385803  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
109394900  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109383211  MYC; myc proto-oncogene protein [KO:K04377]
109393101  GAB1; GRB2-associated-binding protein 1 [KO:K09593]
109373329  NRG3; pro-neuregulin-3, membrane-bound isoform [KO:K05457]
109381238  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109394108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109372681  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109382484  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109395865  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
109373811  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
109381083  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109385878  RAC-beta serine/threonine-protein kinase-like isoform X1 [KO:K04456] [EC:2.7.11.1]
109374859  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109385353  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109381262  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
109379764  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
109384219  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
109393572  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
109384256  BAD; bcl2-associated agonist of cell death [KO:K02158]
109388396  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
109383166  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
109395991  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
hai04010  MAPK signaling pathway
hai04020  Calcium signaling pathway
hai04110  Cell cycle
hai04150  mTOR signaling pathway
hai04151  PI3K-Akt signaling pathway
hai05212  Pancreatic cancer
hai05213  Endometrial cancer
hai05214  Glioma
hai05223  Non-small cell lung cancer
KO pathway
ko04012   
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