KEGG   PATHWAY: dsp04012
Entry
dsp04012                    Pathway                                
Name
ErbB signaling pathway - Dipodomys spectabilis (banner-tailed kangaroo rat)
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
dsp04012  ErbB signaling pathway
dsp04012

Organism
Dipodomys spectabilis (banner-tailed kangaroo rat) [GN:dsp]
Gene
122127051  Egf; pro-epidermal growth factor [KO:K04357]
122125176  Tgfa; protransforming growth factor alpha [KO:K08774]
122106898  Areg; amphiregulin [KO:K09782]
122112209  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
122103204  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
122120202  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
122128054  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
122123175  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
122116510  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
122118130  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
122128350  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
122116145  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
122110671  Prkcg; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
122110362  Cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
122105546  Cblb; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
122103309  signal transducer and activator of transcription 5A-like [KO:K11223]
122100261  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
122120491  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
122125312  Ptk2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
122095902  Crkl; crk-like protein [KO:K04438]
122102190  Crk; adapter molecule crk isoform X1 [KO:K04438]
122108952  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
122103748  Abl2; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
122099865  Nck1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
122121340  Nck2; cytoplasmic protein NCK2 [KO:K19862]
122115583  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
122097055  Pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
122116371  Pak3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
122097586  Pak4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
122120469  Pak5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
122114535  serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
122119529  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
122119668  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
122097824  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
122115378  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
122116492  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122108943  Jun; transcription factor AP-1 [KO:K04448]
122098786  Elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
122106744  Btc; probetacellulin [KO:K09783]
122118157  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
122106918  Ereg; proepiregulin [KO:K09784]
122124201  Erbb3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
122126631  Nrg1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
122118158  Nrg2; pro-neuregulin-2, membrane-bound isoform isoform X1 [KO:K05456]
122107486  Erbb4; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
122109169  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
122122823  Shc2; SHC-transforming protein 2 [KO:K17447]
122113790  Shc3; SHC-transforming protein 3 [KO:K17448]
122114464  Shc4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449]
122128376  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
122104519  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
122106484  Sos2; son of sevenless homolog 2 [KO:K03099]
122095011  Hras; GTPase HRas isoform X1 [KO:K02833]
122098841  Kras; GTPase KRas isoform X1 [KO:K07827]
122118367  Nras; GTPase NRas [KO:K07828]
122098764  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
122105936  Braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
122107826  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122114391  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122099331  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122095844  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122096287  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122102408  Myc; myc proto-oncogene protein [KO:K04377]
122127211  Gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
122116565  Nrg3; pro-neuregulin-3, membrane-bound isoform isoform X1 [KO:K05457]
122123409  Nrg4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
122095294  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122121501  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122107232  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122123339  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like [KO:K00922] [EC:2.7.1.153]
122108047  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122100872  Pik3r2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122117343  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122097416  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122101263  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122126696  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122121508  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
122105362  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
122117335  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
122107645  Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
122105036  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
122096813  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
122101247  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
122111380  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
dsp04010  MAPK signaling pathway
dsp04020  Calcium signaling pathway
dsp04110  Cell cycle
dsp04150  mTOR signaling pathway
dsp04151  PI3K-Akt signaling pathway
dsp05212  Pancreatic cancer
dsp05213  Endometrial cancer
dsp05214  Glioma
dsp05223  Non-small cell lung cancer
KO pathway
ko04012   
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