KEGG   PATHWAY: lmut04012
Entry
lmut04012                   Pathway                                
Name
ErbB signaling pathway - Lagopus muta (rock ptarmigan)
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
lmut04012  ErbB signaling pathway
lmut04012

Organism
Lagopus muta (rock ptarmigan) [GN:lmut]
Gene
125692196  EGF; pro-epidermal growth factor [KO:K04357]
125685318  TGFA; protransforming growth factor alpha [KO:K08774]
125691887  AREG; amphiregulin [KO:K09782]
125696492  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
125684537  ERBB2; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
125690472  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like [KO:K01116] [EC:3.1.4.11]
125701080  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
125699039  PLCG2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
125685190  CAMK2B; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
125692621  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
125693507  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
125700173  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
125702349  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
125700557  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
125703652  CBL; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
125702435  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
125684570  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
125701451  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
125691260  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
125701521  CRKL; crk-like protein [KO:K04438]
125702829  CRK; adapter molecule crk isoform X1 [KO:K04438]
125702456  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
125692813  ABL2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
125687356  NCK2; cytoplasmic protein NCK2 [KO:K19862]
125687950  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
125697448  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
125699845  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
125686366  PAK4; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
125690175  PAK5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
125694453  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
125702281  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
125691554  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125693785  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125700042  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125693900  JUN; transcription factor Jun [KO:K04448]
125692385  BTC; probetacellulin isoform X1 [KO:K09783]
125700392  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
125692489  EREG; proepiregulin [KO:K09784]
125685538  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
125686716  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
125700190  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
125697184  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
125685714  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
125684893  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
125687232  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
125698401  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
125702186  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
125695063  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
125688936  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
125694448  HRAS; GTPase HRas [KO:K02833]
125688361  KRAS; GTPase KRas isoform X1 [KO:K07827]
125684092  NRAS; GTPase NRas [KO:K07828]
125697327  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
125698855  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125698355  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125684996  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125701926  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125691213  MYC; myc proto-oncogene protein [KO:K04377]
125691578  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
125693124  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
125698206  NRG4; pro-neuregulin-4, membrane-bound isoform isoform X1 [KO:K05458]
125697457  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125697863  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125703469  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
125685084  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
125686542  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125694122  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
125689872  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125694568  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125703316  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
125702977  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
125694972  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
125685311  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
125691796  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
125686198  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
125684119  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
125697108  cyclin-dependent kinase inhibitor 1-like 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
lmut04010  MAPK signaling pathway
lmut04020  Calcium signaling pathway
lmut04110  Cell cycle
lmut04150  mTOR signaling pathway
KO pathway
ko04012   
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