KEGG   PATHWAY: lroh04012
Entry
lroh04012                   Pathway                                
Name
ErbB signaling pathway - Labeo rohita (rohu)
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
lroh04012  ErbB signaling pathway
lroh04012

Organism
Labeo rohita (rohu) [GN:lroh]
Gene
127175864  egf; pro-epidermal growth factor [KO:K04357]
127166375  tgfa; protransforming growth factor alpha isoform X1 [KO:K08774]
127176285  egfra; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
127156110  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
127173720  erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
127154337  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
127181164  plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
127169829  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
127171585  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
127165937  camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
127167888  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
127174003  camk2g1; calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
127174722  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
127152422  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
127166764  prkcaa; LOW QUALITY PROTEIN: protein kinase C, alpha, a [KO:K02677] [EC:2.7.11.13]
127163386  prkcab; LOW QUALITY PROTEIN: protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
127160219  prkcbb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
127163312  prkcba; protein kinase C, beta a isoform X1 [KO:K19662] [EC:2.7.11.13]
127178761  prkcg; protein kinase C alpha type [KO:K19663] [EC:2.7.11.13]
127177006  cbl; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
127171620  cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
127155590  stat5a; signal transducer and activator of transcription 5A [KO:K11224]
127174202  stat5b; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
127154786  src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
127178815  ptk2ab; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
127181451  ptk2aa; protein tyrosine kinase 2aa isoform X1 [KO:K05725] [EC:2.7.10.2]
127177264  crk; adapter molecule crk [KO:K04438]
127152559  crkl; crk-like protein [KO:K04438]
127165996  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
127169383  abl2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
127155524  nck1b; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
127183033  nck1a; cytoplasmic protein NCK1 [KO:K07365]
127170904  nck2a; cytoplasmic protein NCK2a [KO:K19862]
127167054  nck2b; LOW QUALITY PROTEIN: cytoplasmic protein NCK2b [KO:K19862]
127180889  pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
127153773  pak2b; serine/threonine-protein kinase PAK 2b isoform X1 [KO:K04410] [EC:2.7.11.1]
127178121  pak2a; serine/threonine-protein kinase PAK 2a [KO:K04410] [EC:2.7.11.1]
127162623  serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
127176800  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
127183356  pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
127179937  serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
127182619  pak6b; serine/threonine-protein kinase PAK 6b [KO:K05735] [EC:2.7.11.1]
127173925  map2k4b; dual specificity mitogen-activated protein kinase kinase 4b isoform X1 [KO:K04430] [EC:2.7.12.2]
127162692  map2k4a; dual specificity mitogen-activated protein kinase kinase 4a isoform X1 [KO:K04430] [EC:2.7.12.2]
127164041  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
127173973  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
127152220  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
127174909  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
127152675  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
127165315  june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
127183046  jun; transcription factor AP-1 [KO:K04448]
127169677  elk1; ETS domain-containing protein Elk-1 [KO:K04375]
127153013  btc; probetacellulin [KO:K09783]
127176614  hbegfa; heparin-binding EGF-like growth factor a [KO:K08523]
127152002  hbegfb; heparin-binding EGF-like growth factor b [KO:K08523]
127154870  erbb3b; receptor tyrosine-protein kinase erbB-3b [KO:K05084] [EC:2.7.10.1]
127166958  erbb3a; receptor tyrosine-protein kinase erbB-3a isoform X1 [KO:K05084] [EC:2.7.10.1]
127171909  nrg1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
127175899  nrg2b; neuregulin 2b isoform X1 [KO:K05456]
127152227  nrg2a; neuregulin 2a isoform X1 [KO:K05456]
127170185  erbb4a; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
127170958  receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
127161874  si:ch73-383l1.1; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
127178036  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
127153208  shc2; SHC-transforming protein 2 isoform X1 [KO:K17447]
127152212  shc3; SHC-transforming protein 3 [KO:K17448]
127167204  grb2a; growth factor receptor-bound protein 2a [KO:K04364]
127160635  grb2b; growth factor receptor-bound protein 2b isoform X1 [KO:K04364]
127172877  sos1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
127174997  sos2; son of sevenless homolog 2 [KO:K03099]
127156808  hrasa; HRas proto-oncogene, GTPase a [KO:K02833]
127168650  hrasb; HRas proto-oncogene, GTPase b [KO:K02833]
127156990  kras; GTPase KRas isoform X1 [KO:K07827]
127160738  zgc:55558; GTPase KRas [KO:K07827]
127169998  nras; GTPase NRas [KO:K07828]
127165632  araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
127163979  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
127154571  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
127172884  raf1b; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
127180735  map2k1; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
127153291  map2k2b; dual specificity mitogen-activated protein kinase kinase 2b [KO:K04369] [EC:2.7.12.2]
127153476  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
127164820  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
127162808  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
127154385  mycb; transcriptional regulator Myc-B [KO:K04377]
127156107  myca; transcriptional regulator Myc-A [KO:K04377]
127168560  gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
127174142  nrg3b; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
127175207  pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
127154480  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
127177108  pik3cb; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
127172737  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
127162255  zgc:158659; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
127176088  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
127164849  pik3r1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
127166520  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
127171830  akt2l; v-akt murine thymoma viral oncogene homolog 2, like [KO:K04456] [EC:2.7.11.1]
127168081  akt3b; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127179883  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127151836  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
127180526  akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127174741  akt3a; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127169200  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
127177545  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
127171970  rps6kb1a; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
127152354  eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
127167836  badb; BCL2 associated agonist of cell death b [KO:K02158]
127153080  bada; bcl2-associated agonist of cell death [KO:K02158]
127170027  gsk3bb; glycogen synthase kinase 3 beta, genome duplicate b [KO:K03083] [EC:2.7.11.26]
127170699  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
127164397  cdkn1ba; cyclin-dependent kinase inhibitor 1Ba [KO:K06624]
127156930  cdkn1bb; cyclin-dependent kinase inhibitor 1Bb [KO:K06624]
127153631  cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
127164043  cdkn1d; cyclin-dependent kinase inhibitor 1D [KO:K06625]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:14967450
  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
PMID:11252954
  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
PMID:16829981
  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
PMID:17000658
  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
PMID:16377102
  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
PMID:14744244
  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
PMID:12851486
  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
PMID:15864276
  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
PMID:16729045
  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
PMID:16729043
  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
PMID:10880430
  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
Bioessays 20:913-21 (1998)
DOI:10.1002/(SICI)1521-1878(199811)20:11<913::AID-BIES6>3.0.CO;2-T
Reference
PMID:15863494
  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
PMID:10490623
  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
lroh04010  MAPK signaling pathway
lroh04020  Calcium signaling pathway
lroh04110  Cell cycle
lroh04150  mTOR signaling pathway
KO pathway
ko04012   
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