KEGG   PATHWAY: clud04012
Entry
clud04012                   Pathway                                
Name
ErbB signaling pathway - Canis lupus dingo (dingo)
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
clud04012  ErbB signaling pathway
clud04012

Organism
Canis lupus dingo (dingo) [GN:clud]
Gene
112671646  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
112674472  TGFA; protransforming growth factor alpha [KO:K08774]
112652277  AREG; amphiregulin [KO:K09782]
112661500  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
112655065  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
112673956  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X3 [KO:K01116] [EC:3.1.4.11]
112646723  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
112671686  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
112650738  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X2 [KO:K04515] [EC:2.7.11.17]
112651229  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
112651948  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
112652873  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
112640230  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
112645036  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
112671204  CBL; E3 ubiquitin-protein ligase CBL isoform X2 [KO:K04707] [EC:2.3.2.27]
112679007  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
112655519  signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
112655520  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
112673919  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
112662017  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
112677583  CRK; adapter molecule crk isoform X1 [KO:K04438]
112677012  CRKL; crk-like protein isoform X1 [KO:K04438]
112677338  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
112648535  ABL2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
112661175  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
112669668  NCK2; cytoplasmic protein NCK2 [KO:K19862]
112642133  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
112676536  PAK2; serine/threonine-protein kinase PAK 2 isoform X1 [KO:K04410] [EC:2.7.11.1]
112649243  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
112645492  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
112673605  PAK5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
112676129  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
112647348  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
112666418  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
112645941  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
112659577  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
112671968  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
112647115  JUN; transcription factor Jun [KO:K04448]
112673250  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
112652395  BTC; probetacellulin isoform X1 [KO:K09783]
112658975  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
112652315  EREG; proepiregulin [KO:K09784]
112678033  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
112644371  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X4 [KO:K05455]
112658920  NRG2; pro-neuregulin-2, membrane-bound isoform isoform X3 [KO:K05456]
112656400  ERBB4; receptor tyrosine-protein kinase erbB-4 isoform X2 [KO:K05085] [EC:2.7.10.1]
112648956  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
112666141  SHC2; SHC-transforming protein 2 isoform X3 [KO:K17447]
112644865  SHC3; SHC-transforming protein 3 [KO:K17448]
112675960  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
112672798  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
112657995  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
112664493  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
112663536  HRAS; GTPase HRas isoform X1 [KO:K02833]
112665533  KRAS; GTPase KRas isoform X1 [KO:K07827]
112664166  NRAS; GTPase NRas [KO:K07828]
112673245  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
112650991  BRAF; serine/threonine-protein kinase B-raf isoform X5 [KO:K04365] [EC:2.7.11.1]
112661394  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112675721  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112666294  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
112640050  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
112677029  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112669083  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
112662261  MYC; myc proto-oncogene protein [KO:K04377]
112669327  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
112651754  NRG3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
112678358  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
112646871  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X5 [KO:K00922] [EC:2.7.1.153]
112661215  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112662621  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112666735  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112660199  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112642563  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
112658031  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112648737  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112645463  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112678102  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
112655510  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
112659290  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
112648317  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
112659359  BAD; bcl2-associated agonist of cell death [KO:K02158]
112677588  GSK3B; glycogen synthase kinase-3 beta isoform X3 [KO:K03083] [EC:2.7.11.26]
112665406  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
112641497  CDKN1A; cyclin-dependent kinase inhibitor 1 [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
clud04010  MAPK signaling pathway
clud04020  Calcium signaling pathway
clud04110  Cell cycle
clud04150  mTOR signaling pathway
clud04151  PI3K-Akt signaling pathway
clud05212  Pancreatic cancer
clud05213  Endometrial cancer
clud05214  Glioma
clud05223  Non-small cell lung cancer
KO pathway
ko04012   
LinkDB

DBGET integrated database retrieval system