KEGG   PATHWAY: sasa04012
sasa04012                   Pathway                                

ErbB signaling pathway - Salmo salar (Atlantic salmon)
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.
Environmental Information Processing; Signal transduction
Pathway map
sasa04012  ErbB signaling pathway

Salmo salar (Atlantic salmon) [GN:sasa]
106611584  egf; epidermal growth factor [KO:K04357]
106565349  protransforming growth factor alpha-like [KO:K08774]
106583550  protransforming growth factor alpha-like [KO:K08774]
106600426  epidermal growth factor receptor-like [KO:K04361] [EC:]
106569312  epidermal growth factor receptor-like [KO:K04361] [EC:]
106579586  melanoma receptor tyrosine-protein kinase-like [KO:K04361] [EC:]
106590362  melanoma receptor tyrosine-protein kinase-like [KO:K04361] [EC:]
106579080  erbb2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:]
106566556  plcg1; phospholipase C gamma 1 [KO:K01116] [EC:]
106560399  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like [KO:K01116] [EC:]
106573684  plcg2; phospholipase C gamma 2 [KO:K05859] [EC:]
106606853  calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:]
106569240  calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:]
106602935  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:]
100380644  kcc2d; calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:]
106562908  calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:]
106597964  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106597932  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106563741  calcium/calmodulin-dependent protein kinase type II subunit alpha-like [KO:K04515] [EC:]
106597963  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
100380658  kcc2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:]
106597631  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106597965  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106597934  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106576966  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:]
106577507  calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:]
106584897  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:]
106597904  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106597817  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106597116  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106597790  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106589429  calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:]
106597844  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106597935  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:]
106564882  protein kinase C alpha type [KO:K02677] [EC:]
106594520  protein kinase C beta type [KO:K19662] [EC:]
106563990  protein kinase C beta type-like [KO:K19662] [EC:]
106563994  protein kinase C beta type-like [KO:K19662] [EC:]
106593748  protein kinase C beta type-like [KO:K19662] [EC:]
106603416  E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:]
106567671  E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:]
106612473  cbl; Cbl proto-oncogene [KO:K04707] [EC:]
106602828  cblb; Cbl proto-oncogene B [KO:K22517] [EC:]
106607295  signal transducer and activator of transcription 5B-like [KO:K11224]
100380532  sta5b; Signal transducer and activator of transcription 5B [KO:K11224]
106579144  signal transducer and activator of transcription 5B-like [KO:K11224]
106565074  proto-oncogene tyrosine-protein kinase Src-like [KO:K05704] [EC:]
106572626  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:]
106567112  proto-oncogene tyrosine-protein kinase Src-like [KO:K05704] [EC:]
106583686  proto-oncogene tyrosine-protein kinase Src-like [KO:K05704] [EC:]
106570401  focal adhesion kinase 1-like [KO:K05725] [EC:]
106588992  focal adhesion kinase 1-like [KO:K05725] [EC:]
106566436  crk-like protein [KO:K04438]
106603721  adapter molecule crk-like [KO:K04438]
106563168  crk-like protein [KO:K04438]
106580783  adapter molecule crk-like [KO:K04438]
106567578  adapter molecule crk-like [KO:K04438]
100306842  crk; v-crk sarcoma virus CT10 oncogene homolog (avian) [KO:K04438]
106566947  tyrosine-protein kinase ABL1-like [KO:K06619] [EC:]
106563284  tyrosine-protein kinase ABL1-like [KO:K06619] [EC:]
106613905  abl2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO:K08887] [EC:]
106584319  Abelson tyrosine-protein kinase 2-like [KO:K08887] [EC:]
106579755  cytoplasmic protein NCK1-like [KO:K07365]
106590688  cytoplasmic protein NCK1-like [KO:K07365]
106575249  cytoplasmic protein NCK2-like [KO:K19862]
106581983  cytoplasmic protein NCK2-like [KO:K19862]
106574449  cytoplasmic protein NCK2-like [KO:K19862]
106586771  nck2; NCK adaptor protein 2 [KO:K19862]
100380347  pak3; Serine/threonine-protein kinase PAK 3 [KO:K04409] [EC:]
106612881  serine/threonine-protein kinase PAK 1-like [KO:K04409] [EC:]
106595470  serine/threonine-protein kinase PAK 2-like [KO:K04410] [EC:]
106594148  serine/threonine-protein kinase PAK 2-like [KO:K04410] [EC:]
106595887  serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:]
106584354  serine/threonine-protein kinase PAK 2-like [KO:K04410] [EC:]
106613860  pak2; p21 (RAC1) activated kinase 2 [KO:K04410] [EC:]
106603108  serine/threonine-protein kinase PAK 3-like [KO:K05733] [EC:]
106563430  serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:]
106580861  serine/threonine-protein kinase PAK 4-like [KO:K05734] [EC:]
106612596  serine/threonine-protein kinase PAK 4-like [KO:K05734] [EC:]
106571559  serine/threonine-protein kinase PAK 7-like [KO:K05736] [EC:]
106608064  serine/threonine-protein kinase PAK 7-like [KO:K05736] [EC:]
106581963  serine/threonine-protein kinase PAK 6-like [KO:K05735] [EC:]
106610869  serine/threonine-protein kinase PAK 6-like [KO:K05735] [EC:]
106571135  serine/threonine-protein kinase PAK 6-like [KO:K05735] [EC:]
106601504  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:]
106578855  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:]
106589490  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:]
100196891  map2k4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:]
106587435  dual specificity mitogen-activated protein kinase kinase 7-like [KO:K04431] [EC:]
106564723  dual specificity mitogen-activated protein kinase kinase 7-like [KO:K04431] [EC:]
106604288  mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
106560362  mitogen-activated protein kinase 10 [KO:K04440] [EC:]
106604910  mitogen-activated protein kinase 9-like [KO:K04440] [EC:]
106568502  mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
106576863  mitogen-activated protein kinase 8-like [KO:K04440] [EC:]
106579004  mitogen-activated protein kinase 8 [KO:K04440] [EC:]
106563760  mitogen-activated protein kinase 9-like [KO:K04440] [EC:]
106589346  mitogen-activated protein kinase 8-like [KO:K04440] [EC:]
106600411  jun; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
106613963  JUN; transcription factor AP-1-like [KO:K04448]
106569413  transcription factor AP-1-like [KO:K04448]
106568560  transcription factor AP-1-like [KO:K04448]
106584280  JUN; transcription factor AP-1-like [KO:K04448]
106572830  transcription factor AP-1-like [KO:K04448]
106566498  ETS domain-containing protein Elk-1-like [KO:K04375]
106563612  probetacellulin-like [KO:K09783]
106568258  probetacellulin-like [KO:K09783]
100286490  hbegf; Proheparin-binding EGF-like growth factor [KO:K08523]
106604317  proheparin-binding EGF-like growth factor [KO:K08523]
106603916  proheparin-binding EGF-like growth factor [KO:K08523]
106612135  proheparin-binding EGF-like growth factor [KO:K08523]
100286458  ereg; Proepiregulin [KO:K09784]
106567054  receptor tyrosine-protein kinase erbB-3-like [KO:K05084] [EC:]
106572678  receptor tyrosine-protein kinase erbB-3-like [KO:K05084] [EC:]
106565537  receptor tyrosine-protein kinase erbB-3-like [KO:K05084] [EC:]
106583220  receptor tyrosine-protein kinase erbB-3-like [KO:K05084] [EC:]
106571385  nrg1; neuregulin 1 [KO:K05455]
106604398  pro-neuregulin-2, membrane-bound isoform-like [KO:K05456]
106602814  pro-neuregulin-2, membrane-bound isoform-like [KO:K05456]
106563662  pro-neuregulin-2, membrane-bound isoform-like [KO:K05456]
106612118  nrg2; neuregulin 2 [KO:K05456]
106603019  pro-neuregulin-2, membrane-bound isoform-like [KO:K05456]
106575810  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:]
106592198  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:]
106586446  receptor tyrosine-protein kinase erbB-4-like [KO:K05085] [EC:]
106582203  erbb4; erb-b2 receptor tyrosine kinase 4 [KO:K05085] [EC:]
106575570  SHC-transforming protein 1-like [KO:K06279]
106593005  SHC-transforming protein 1-like [KO:K06279]
106613792  SHC-transforming protein 2-like [KO:K17447]
106584416  SHC-transforming protein 2-like [KO:K17447]
106568489  shc3; SHC adaptor protein 3 [KO:K17448]
106587111  growth factor receptor-bound protein 2-like [KO:K04364]
106607067  growth factor receptor-bound protein 2 [KO:K04364]
106564671  growth factor receptor-bound protein 2-like [KO:K04364]
100306767  grb2; growth factor receptor-bound protein 2 [KO:K04364]
106601599  sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
106584773  son of sevenless homolog 1-like [KO:K03099]
106611443  son of sevenless homolog 2-like [KO:K03099]
106564790  son of sevenless homolog 1-like [KO:K03099]
106573361  GTPase HRas-like [KO:K02833]
100196603  rash; GTPase HRas [KO:K02833]
106601908  GTPase HRas-like [KO:K07827]
106606379  GTPase HRas-like [KO:K07827]
106561428  GTPase KRas [KO:K07827]
100380437  rask; GTPase KRas [KO:K07827]
106580530  serine/threonine-protein kinase A-Raf-like [KO:K08845] [EC:]
106585138  serine/threonine-protein kinase A-Raf-like [KO:K08845] [EC:]
106571905  RAF1b; RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:]
106566757  RAF1a; RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:]
100136351  raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:]
106584829  map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
106600441  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:]
106613775  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
106569535  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:]
100194780  mp2k2; Dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
106570952  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
106600714  mitogen-activated protein kinase 1-like [KO:K04371] [EC:]
106592057  mitogen-activated protein kinase 1-like [KO:K04371] [EC:]
100380511  mk03; Mitogen-activated protein kinase 3 [KO:K04371] [EC:]
106568625  myc; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
106578682  transcriptional regulator Myc-like [KO:K04377]
100380346  myc2; Transcriptional regulator Myc-2 [KO:K04377]
106590162  c-myc; transcriptional regulator Myc [KO:K04377]
100380531  myc; Viral myc transforming protein [KO:K04377]
106602350  GRB2-associated-binding protein 1-like [KO:K09593]
100380732  gab1; GRB2-associated-binding protein 1 [KO:K09593]
106578202  gab1; GRB2 associated binding protein 1 [KO:K09593]
106607935  pro-neuregulin-3, membrane-bound isoform-like [KO:K05457]
106578362  pro-neuregulin-3, membrane-bound isoform-like [KO:K05457]
106579414  pro-neuregulin-3, membrane-bound isoform-like [KO:K05457]
106577125  pro-neuregulin-3, membrane-bound isoform-like [KO:K05457]
106573528  nrg4; neuregulin 4 [KO:K05458]
100195785  nrg4; Pro-neuregulin-4, membrane-bound isoform [KO:K05458]
106598808  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:]
106568747  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:]
106572046  pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
106581359  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform-like [KO:K00922] [EC:]
106613931  pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
106613172  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform-like [KO:K00922] [EC:]
106600405  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
106567700  phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
106599005  phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649]
106560529  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
106613635  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
106569403  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
106568949  phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649]
106573900  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
106563018  phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649]
106584012  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
106587034  phosphatidylinositol 3-kinase regulatory subunit alpha-like [KO:K02649]
106582637  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:]
106585772  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:]
106602915  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:]
106607890  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:]
106610858  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:]
106564869  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:]
106613111  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:]
106581334  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
106571474  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
100194605  akt2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:]
106589689  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
100380849  mtor; mechanistic target of rapamycin [KO:K07203] [EC:]
106602694  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:]
106603521  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:]
106609967  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:]
106613000  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:]
106581130  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:]
106567964  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:]
106580340  4EBP2; eukaryotic translation initiation factor 4E-binding protein 2-like [KO:K07205]
106585258  4EBP2; eukaryotic translation initiation factor 4E-binding protein 2-like [KO:K07205]
106603152  BAD; bcl2-associated agonist of cell death-like [KO:K02158]
106578087  bcl2-associated agonist of cell death-like [KO:K02158]
106563493  BAD; bcl2-associated agonist of cell death-like [KO:K02158]
106574304  glycogen synthase kinase-3 beta-like [KO:K03083] [EC:]
106582120  gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
106586650  glycogen synthase kinase-3 beta [KO:K03083] [EC:]
106575154  glycogen synthase kinase-3 beta-like [KO:K03083] [EC:]
106609100  cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
106575072  CDN1B; cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
106560990  cdkn1b; cyclin dependent kinase inhibitor 1B [KO:K06624]
106584490  CDN1B; cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
106565657  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
106583085  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Marmor MD, Skaria KB, Yarden Y.
Signal transduction and oncogenesis by ErbB/HER receptors.
Int J Radiat Oncol Biol Phys 58:903-13 (2004)
Yarden Y, Sliwkowski MX.
Untangling the ErbB signalling network.
Nat Rev Mol Cell Biol 2:127-37 (2001)
Citri A, Yarden Y.
EGF-ERBB signalling: towards the systems level.
Nat Rev Mol Cell Biol 7:505-16 (2006)
Scaltriti M, Baselga J.
The epidermal growth factor receptor pathway: a model for targeted therapy.
Clin Cancer Res 12:5268-72 (2006)
Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS.
Epidermal growth factor receptor (EGFR) signaling in cancer.
Gene 366:2-16 (2006)
Holbro T, Hynes NE.
ErbB receptors: directing key signaling networks throughout life.
Annu Rev Pharmacol Toxicol 44:195-217 (2004)
Liang J, Slingerland JM.
Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.
Cell Cycle 2:339-45 (2003)
Hynes NE, Lane HA.
ERBB receptors and cancer: the complexity of targeted inhibitors.
Nat Rev Cancer 5:341-54 (2005)
Oda K, Matsuoka Y, Funahashi A, Kitano H.
A comprehensive pathway map of epidermal growth factor receptor signaling.
Mol Syst Biol 1:2005.0010 (2005)
Schulze WX, Deng L, Mann M.
Phosphotyrosine interactome of the ErbB-receptor kinase family.
Mol Syst Biol 1:2005.0008 (2005)
Olayioye MA, Neve RM, Lane HA, Hynes NE.
The ErbB signaling network: receptor heterodimerization in development and cancer.
EMBO J 19:3159-67 (2000)
McCarty JH.
The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.
Clark DE, Williams CC, Duplessis TT, Moring KL, Notwick AR, Long W, Lane WS, Beuvink I, Hynes NE, Jones FE.
ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.
J Biol Chem 280:24175-80 (2005)
Muthuswamy SK, Gilman M, Brugge JS.
Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.
Mol Cell Biol 19:6845-57 (1999)
Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda M.
Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.
J Biol Chem 273:17186-91 (1998)
sasa04010  MAPK signaling pathway
sasa04020  Calcium signaling pathway
sasa04110  Cell cycle
sasa04150  mTOR signaling pathway
KO pathway

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