KEGG   PATHWAY: cery04012
Entry
cery04012                   Pathway                                
Name
ErbB signaling pathway - Chanodichthys erythropterus (predatory carp)
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
cery04012  ErbB signaling pathway
cery04012

Organism
Chanodichthys erythropterus (predatory carp) [GN:cery]
Gene
137002638  nck1a; SH2/SH3 adapter protein Nck1 [KO:K07365]
137002917  mycb; transcriptional regulator Myc-B [KO:K04377]
137002995  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
137003113  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
137003636  egfra; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
137003657  pak2a; serine/threonine-protein kinase PAK 2a [KO:K04410] [EC:2.7.11.1]
137004124  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
137004407  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
137004487  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
137004517  crk; adapter molecule crk [KO:K04438]
137004988  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
137006461  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
137006865  [KO:K05735] [EC:2.7.11.1]
137007326  erbb2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
137007341  camk2g1; calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
137007419  stat5b; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
137007833  map2k4b; dual specificity mitogen-activated protein kinase kinase 4b isoform X1 [KO:K04430] [EC:2.7.12.2]
137008162  nrg3b; pro-neuregulin-3, membrane-bound isoform [KO:K05457]
137008268  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
137008704  erbb3b; receptor tyrosine-protein kinase erbB-3b [KO:K05084] [EC:2.7.10.1]
137008711  src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
137008719  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
137009720  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
137009724  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
137009787  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
137010730  prkcaa; protein kinase C, alpha, a [KO:K02677] [EC:2.7.11.13]
137010950  grb2a; growth factor receptor-bound protein 2a isoform X1 [KO:K04364]
137011258  tgfa; protransforming growth factor alpha [KO:K08774]
137011670  nck2b; cytoplasmic protein NCK2b [KO:K19862]
137011682  erbb3a; receptor tyrosine-protein kinase erbB-3a isoform X1 [KO:K05084] [EC:2.7.10.1]
137011727  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
137012019  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
137012088  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
137012171  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
137012342  eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
137012606  nrg2a; neuregulin 2a isoform X1 [KO:K05456]
137012659  btc; probetacellulin [KO:K09783]
137012800  hbegfb; heparin-binding EGF-like growth factor b [KO:K08523]
137012826  shc3; SHC-transforming protein 3 [KO:K17448]
137012850  bada; uncharacterized protein bada [KO:K02158]
137012972  crkl; crk-like protein [KO:K04438]
137013462  [KO:K04361] [EC:2.7.10.1]
137013555  myca; transcriptional regulator Myc-A [KO:K04377]
137014056  nck1b; SH2/SH3 adapter protein Nck1 isoform X1 [KO:K07365]
137014687  hrasa; HRas proto-oncogene, GTPase a isoform X1 [KO:K02833]
137015007  cdkn1bb; cyclin dependent kinase inhibitor 1Bb [KO:K06624]
137015259  egf; pro-epidermal growth factor [KO:K04357]
137015453  [KO:K05458]
137015480  kras; GTPase KRas isoform X1 [KO:K07827]
137017221  map2k4a; dual specificity mitogen-activated protein kinase kinase 4a isoform X1 [KO:K04430] [EC:2.7.12.2]
137017360  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
137017475  zgc:55558; GTPase KRas [KO:K07827]
137017505  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
137017671  hbegfa; heparin-binding EGF-like growth factor a [KO:K08523]
137017725  prkcbb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
137018000  prkcab; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
137018700  [KO:K04456] [EC:2.7.11.1]
137019264  pak6b; serine/threonine-protein kinase PAK 6b isoform X1 [KO:K05735] [EC:2.7.11.1]
137019291  pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
137019377  jun; transcription factor AP-1 [KO:K04448]
137020024  [KO:K05457]
137020449  nrg2b; neuregulin 2b isoform X1 [KO:K05456]
137020466  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
137020496  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
137020639  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
137020722  sos2; son of sevenless homolog 2 [KO:K03099]
137021365  sos1; son of sevenless homolog 1 [KO:K03099]
137021461  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
137021787  raf1b; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
137022705  pak1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
137023110  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
137023276  plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
137023351  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
137024359  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
137024465  cdkn1ba; cyclin-dependent kinase inhibitor 1Ba [KO:K06624]
137024651  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
137025670  prkcg; protein kinase C alpha type [KO:K19663] [EC:2.7.11.13]
137026734  mtor; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
137026861  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
137026886  nras; GTPase NRas [KO:K07828]
137026924  abl2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
137027760  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
137028087  pak2b; serine/threonine-protein kinase PAK 2b isoform X1 [KO:K04410] [EC:2.7.11.1]
137028469  akt2l; v-akt murine thymoma viral oncogene homolog 2, like [KO:K04456] [EC:2.7.11.1]
137028537  [KO:K04515] [EC:2.7.11.17]
137028712  cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
137028719  rps6kb1a; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
137028960  nrg1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
137029156  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
137029320  cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
137030139  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
137030221  [KO:K02158]
137031219  hrasb; HRas proto-oncogene, GTPase b [KO:K02833]
137031449  erbb4a; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
137031545  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
137031622  gsk3bb; glycogen synthase kinase 3 beta, genome duplicate b isoform X1 [KO:K03083] [EC:2.7.11.26]
137031976  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
137032154  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
137032937  [KO:K05085] [EC:2.7.10.1]
137033110  prkcba; protein kinase C, beta a isoform X1 [KO:K19662] [EC:2.7.11.13]
137033118  gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
137033586  mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
137033664  [KO:K05733] [EC:2.7.11.1]
137033676  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
137033785  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
137033820  camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
137034192  ptk2ab; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
137034610  june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
137035124  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
137035332  [KO:K05085] [EC:2.7.10.1]
137035868  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
137036299  nck2a; cytoplasmic protein NCK2a isoform X1 [KO:K19862]
137036344  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
137037504  ptk2aa; protein tyrosine kinase 2aa isoform X1 [KO:K05725] [EC:2.7.10.2]
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
cery04010  MAPK signaling pathway
cery04020  Calcium signaling pathway
cery04110  Cell cycle
cery04150  mTOR signaling pathway
KO pathway
ko04012   

DBGET integrated database retrieval system