KEGG   PATHWAY: mun04012
Entry
mun04012                    Pathway                                
Name
ErbB signaling pathway - Meriones unguiculatus (Mongolian gerbil)
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
mun04012  ErbB signaling pathway
mun04012

Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110539539  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
110540522  Pak5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
110540535  Cblb; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
110540777  Erbb4; receptor tyrosine-protein kinase erbB-4 isoform X1 [KO:K05085] [EC:2.7.10.1]
110541384  Pak3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
110541705  Araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
110542391  Ptk2; focal adhesion kinase 1 isoform X4 [KO:K05725] [EC:2.7.10.2]
110543001  Elk1; ETS domain-containing protein Elk-1 [KO:K04375]
110544642  [KO:K07828]
110544765  Nras; GTPase NRas [KO:K07828]
110545779  Braf; serine/threonine-protein kinase B-raf isoform X8 [KO:K04365] [EC:2.7.11.1]
110546095  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X8 [KO:K04515] [EC:2.7.11.17]
110546586  Cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
110546686  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X3 [KO:K04515] [EC:2.7.11.17]
110547073  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
110547163  Tgfa; protransforming growth factor alpha [KO:K08774]
110547315  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
110547367  Crk; adapter molecule crk isoform X1 [KO:K04438]
110547825  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110548161  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110548394  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110549145  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110549818  Nrg1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
110550200  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
110550263  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
110550597  Pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
110550814  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
110550874  [KO:K11223]
110550889  [KO:K11224]
110550937  Shc4; SHC-transforming protein 4 [KO:K17449]
110551008  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
110551355  Shc2; SHC-transforming protein 2 isoform X4 [KO:K17447]
110551574  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
110551603  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110551994  Nrg4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
110551996  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X2 [KO:K04515] [EC:2.7.11.17]
110552225  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
110552285  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110552542  Pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
110552794  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
110553196  Egf; pro-epidermal growth factor [KO:K04357]
110553293  Pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
110553683  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110553742  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110553931  Hras; GTPase HRas isoform X1 [KO:K02833]
110555024  Nck1; cytoplasmic protein NCK1 isoform X2 [KO:K07365]
110555335  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
110555390  Gsk3b; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
110555404  Gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
110555605  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110556016  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
110556252  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110556913  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110557378  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
110557386  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110558788  Btc; probetacellulin [KO:K09783]
110558913  Kras; GTPase KRas isoform X1 [KO:K07827]
110558915  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110559000  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110559035  Nck2; cytoplasmic protein NCK2 [KO:K19862]
110559069  Shc3; SHC-transforming protein 3 [KO:K17448]
110559213  Crkl; crk-like protein [KO:K04438]
110559383  Erbb3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
110559612  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110559727  Jun; transcription factor Jun [KO:K04448]
110560064  Myc; myc proto-oncogene protein [KO:K04377]
110560146  Areg; amphiregulin [KO:K09782]
110560360  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
110562581  Cbl; E3 ubiquitin-protein ligase CBL isoform X2 [KO:K04707] [EC:2.3.2.27]
110562875  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110562952  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
110563282  Abl2; tyrosine-protein kinase ABL2 isoform X2 [KO:K08887] [EC:2.7.10.2]
110563512  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110564250  Nrg2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
110564467  Nrg3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110565112  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110565263  Ereg; proepiregulin [KO:K09784]
110565513  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
110566227  Src; proto-oncogene tyrosine-protein kinase Src isoform X2 [KO:K05704] [EC:2.7.10.2]
132650544  Map2k7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
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
mun04010  MAPK signaling pathway
mun04020  Calcium signaling pathway
mun04110  Cell cycle
mun04150  mTOR signaling pathway
mun04151  PI3K-Akt signaling pathway
mun05212  Pancreatic cancer
mun05213  Endometrial cancer
mun05214  Glioma
mun05223  Non-small cell lung cancer
KO pathway
ko04012   

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