KEGG   PATHWAY: ifu04012
Entry
ifu04012                    Pathway                                
Name
ErbB signaling pathway - Ictalurus furcatus (blue catfish)
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
ifu04012  ErbB signaling pathway
ifu04012

Organism
Ictalurus furcatus (blue catfish) [GN:ifu]
Gene
128612081  egf; pro-epidermal growth factor isoform X1 [KO:K04357]
128614915  tgfa; protransforming growth factor alpha isoform X1 [KO:K08774]
128624292  egfra; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
128617463  erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
128619938  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
128606925  plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
128622169  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
128604118  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
128620648  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
128609903  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
128616562  camk2g1; calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
128605908  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
128599012  camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
128615331  prkcaa; protein kinase C, alpha, a [KO:K02677] [EC:2.7.11.13]
128625389  prkcab; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
128622033  prkcbb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
128601966  prkcba; protein kinase C, beta a isoform X1 [KO:K19662] [EC:2.7.11.13]
128608413  prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
128621799  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
128620290  cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
128616839  stat5b; signal transducer and activator of transcription 5B [KO:K11224]
128601883  stat5a; signal transducer and activator of transcription 5A isoform X1 [KO:K11224]
128619070  src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
128625020  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
128610049  ptk2ab; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
128600648  ptk2aa; protein tyrosine kinase 2aa isoform X1 [KO:K05725] [EC:2.7.10.2]
128622105  crkl; crk-like protein [KO:K04438]
128621277  crk; adapter molecule crk [KO:K04438]
128603720  adapter molecule crk-like [KO:K04438]
128603323  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
128607991  abl2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
128614881  nck1b; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
128609101  nck2a; cytoplasmic protein NCK2a [KO:K19862]
128615515  nck2b; cytoplasmic protein NCK2b [KO:K19862]
128606918  pak1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
128613850  pak2b; serine/threonine-protein kinase PAK 2b [KO:K04410] [EC:2.7.11.1]
128609852  pak2a; serine/threonine-protein kinase PAK 2a isoform X1 [KO:K04410] [EC:2.7.11.1]
128620961  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
128601577  pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
128612845  serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
128600891  pak6b; serine/threonine-protein kinase PAK 6b [KO:K05735] [EC:2.7.11.1]
128615580  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
128616832  map2k4b; dual specificity mitogen-activated protein kinase kinase 4b isoform X1 [KO:K04430] [EC:2.7.12.2]
128601752  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
128622154  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
128622257  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
128616632  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
128605628  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
128610446  transcription factor Jun-like [KO:K04448]
128601161  jun; transcription factor AP-1 [KO:K04448]
128603833  june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
128608161  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
128622751  btc; probetacellulin isoform X1 [KO:K09783]
128622129  hbegfb; heparin-binding EGF-like growth factor b [KO:K08523]
128611952  hbegfa; heparin-binding EGF-like growth factor a [KO:K08523]
128619208  erbb3b; receptor tyrosine-protein kinase erbB-3b [KO:K05084] [EC:2.7.10.1]
128614590  erbb3a; receptor tyrosine-protein kinase erbB-3a isoform X1 [KO:K05084] [EC:2.7.10.1]
128620137  nrg1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
128622111  nrg2a; neuregulin 2a isoform X1 [KO:K05456]
128611503  nrg2b; neuregulin 2b [KO:K05456]
128608488  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:2.7.10.1]
128602046  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:2.7.10.1]
128602367  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:2.7.10.1]
128607170  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
128613975  shc2; SHC-transforming protein 2 [KO:K17447]
128622479  shc3; SHC-transforming protein 3 [KO:K17448]
128616031  grb2a; growth factor receptor-bound protein 2a [KO:K04364]
128599154  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
128614273  sos1; son of sevenless homolog 1 [KO:K03099]
128618140  hrasa; HRas proto-oncogene, GTPase a [KO:K02833]
128602959  hrasb; HRas proto-oncogene, GTPase b [KO:K02833]
128618149  kras; GTPase KRas isoform X1 [KO:K07827]
128601824  zgc:55558; GTPase KRas [KO:K07827]
128608137  nras; GTPase NRas [KO:K07828]
128625606  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
128623239  braf; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
128619536  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
128624988  raf1b; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128606701  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128613746  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
128624239  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
128602235  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128625408  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128609564  mycb; transcriptional regulator Myc-B [KO:K04377]
128599743  myca; transcriptional regulator Myc-A [KO:K04377]
128606062  gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
128617705  pro-neuregulin-4, membrane-bound isoform-like [KO:K05458]
128613582  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128619025  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128619253  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
128623950  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
128614576  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
128603480  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
128613234  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128606850  akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
128605437  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128601820  akt3b; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
128607588  mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
128604393  ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
128621550  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
128622585  eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
128622039  bada; uncharacterized protein bada [KO:K02158]
128610063  badb; BCL2 associated agonist of cell death b [KO:K02158]
128608684  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
128601885  gsk3bb; glycogen synthase kinase 3 beta, genome duplicate b [KO:K03083] [EC:2.7.11.26]
128618199  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
128623322  cdkn1ba; cyclin-dependent kinase inhibitor 1Ba [KO:K06624]
128624820  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
ifu04010  MAPK signaling pathway
ifu04020  Calcium signaling pathway
ifu04110  Cell cycle
ifu04150  mTOR signaling pathway
KO pathway
ko04012   
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