KEGG   PATHWAY: mze04012
Entry
mze04012                    Pathway                                

Name
ErbB signaling pathway - Maylandia zebra (zebra mbuna)
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
mze04012  ErbB signaling pathway
mze04012

Organism
Maylandia zebra (zebra mbuna) [GN:mze]
Gene
101487082  egf; pro-epidermal growth factor [KO:K04357]
101486967  tgfa; protransforming growth factor alpha isoform X1 [KO:K08774]
101481239  proheparin-binding EGF-like growth factor [KO:K09782]
101477281  melanoma receptor tyrosine-protein kinase [KO:K04361] [EC:2.7.10.1]
101483528  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
101482712  erbb2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
101473405  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
101470576  plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
101479429  plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101466566  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
101480272  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101475499  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X5 [KO:K04515] [EC:2.7.11.17]
101479352  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
101474026  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101473593  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101472930  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
112429915  calcium/calmodulin-dependent protein kinase type II delta chain-like isoform X1 [KO:K04515] [EC:2.7.11.17]
101487097  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101464257  prkca; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101465488  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101478005  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101481445  protein kinase C alpha type-like [KO:K19663] [EC:2.7.11.13]
101471367  E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
101484693  E3 ubiquitin-protein ligase CBL-like [KO:K04707] [EC:2.3.2.27]
101465135  cbl; E3 ubiquitin-protein ligase CBL isoform X2 [KO:K04707] [EC:2.3.2.27]
101484242  cblb; E3 ubiquitin-protein ligase CBL-B isoform X2 [KO:K22517] [EC:2.3.2.27]
101485426  signal transducer and activator of transcription 5B [KO:K11224]
101468393  signal transducer and activator of transcription 5B [KO:K11224]
101476411  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101479745  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101470907  adapter molecule crk [KO:K04438]
101472174  crkl; crk-like protein [KO:K04438]
101468680  adapter molecule crk [KO:K04438]
101475377  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
101486332  abl2; Abelson tyrosine-protein kinase 2 isoform X1 [KO:K08887] [EC:2.7.10.2]
101479403  nck1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
101465176  nck2; cytoplasmic protein NCK2 [KO:K19862]
101483196  pak1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
101482829  pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
101473947  serine/threonine-protein kinase PAK 2 isoform X1 [KO:K04410] [EC:2.7.11.1]
101484450  serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
101465929  serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
101463583  pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
101464122  serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
101475185  pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
101478377  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
101483027  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
101475777  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101480702  mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101486303  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101477577  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101476882  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101463670  transcription factor AP-1 [KO:K04448]
101486839  jun; transcription factor AP-1 [KO:K04448]
101472459  transcription factor AP-1 [KO:K04448]
101482089  ETS domain-containing protein Elk-1 [KO:K04375]
101468669  probetacellulin isoform X1 [KO:K09783]
101471223  proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
101481723  proepiregulin [KO:K09784]
101465105  receptor tyrosine-protein kinase erbB-3 isoform X2 [KO:K05084] [EC:2.7.10.1]
101469990  receptor tyrosine-protein kinase erbB-3 isoform X1 [KO:K05084] [EC:2.7.10.1]
101480242  pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
101470250  pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
101467929  erbb4; receptor tyrosine-protein kinase erbB-4 isoform X3 [KO:K05085] [EC:2.7.10.1]
101478875  receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
101480827  shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
101463941  SHC-transforming protein 2 isoform X1 [KO:K17447]
101471658  SHC-transforming protein 3 [KO:K17448]
101474172  shc4; SHC-transforming protein 4 isoform X1 [KO:K17449]
101467818  grb2; growth factor receptor-bound protein 2 [KO:K04364]
101477192  GRB2-related adaptor protein 2 isoform X1 [KO:K04364]
101471030  sos2; son of sevenless homolog 2 [KO:K03099]
101471853  sos1; son of sevenless homolog 1 [KO:K03099]
101474892  hras; GTPase HRas [KO:K02833]
101465888  kras; GTPase KRas isoform X1 [KO:K07827]
101485266  GTPase HRas [KO:K07827]
101471760  serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101476445  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
101470685  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101465184  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101484555  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101478402  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101486997  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101474234  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101464606  transcriptional regulator Myc-2 isoform X1 [KO:K04377]
101479046  transcriptional regulator Myc-A [KO:K04377]
101474120  myc; myc proto-oncogene protein [KO:K04377]
101473094  GRB2-associated-binding protein 1 [KO:K09593]
101471751  gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
101464707  nrg3; pro-neuregulin-3, membrane-bound isoform isoform X2 [KO:K05457]
101474689  nrg4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
101466374  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101473981  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101474114  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101469095  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101487871  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101463777  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101478000  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101464472  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101484093  pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101481450  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101470898  pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101467814  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101480630  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101469973  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101476427  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101466452  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101471360  mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101485102  ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
101465875  ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101478146  ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
101475717  eukaryotic translation initiation factor 4E-binding protein 2 [KO:K07205]
101471989  eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
101483296  bad; bcl2-associated agonist of cell death [KO:K02158]
101487930  gsk3b; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
101468035  cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101466273  cyclin-dependent kinase inhibitor 1B [KO:K06624]
101474553  cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
101467117  cyclin-dependent kinase inhibitor 1 isoform X1 [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
mze04010  MAPK signaling pathway
mze04020  Calcium signaling pathway
mze04110  Cell cycle
mze04150  mTOR signaling pathway
KO pathway
ko04012   
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