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KEGG   PATHWAY: xla04012
Entry
xla04012                    Pathway                                
Name
ErbB signaling pathway - Xenopus laevis (African clawed frog)
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
xla04012  ErbB signaling pathway
xla04012

Organism
Xenopus laevis (African clawed frog) [GN:xla]
Gene
100190767  elk1.S; ELK1, member of ETS oncogene family S homeolog [KO:K04375]
100505423  [KO:K07827]
108695799  [KO:K05457]
108696257  camk2g.L; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
108696277  XB5893022.L; protransforming growth factor alpha isoform X1 [KO:K08774]
108696363  [KO:K07203] [EC:2.7.11.1]
108696776  [KO:K19663] [EC:2.7.11.13]
108697792  kras.S; GTPase HRas [KO:K07827]
108697820  [KO:K19663] [EC:2.7.11.13]
108698108  elk1.L; ETS domain-containing protein Elk-1 isoform X2 [KO:K04375]
108698752  sos2.L; son of sevenless homolog 2 isoform X2 [KO:K03099]
108698803  [KO:K04456] [EC:2.7.11.1]
108699252  pak6.L; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
108699793  sos2.S; son of sevenless homolog 2 [KO:K03099]
108699954  abl1.S; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
108700104  pak3.S; serine/threonine-protein kinase PAK 3-like isoform X2 [KO:K05733] [EC:2.7.11.1]
108700290  pak4.S; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
108700316  pak6.S; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
108700442  shc1.S; SHC-transforming protein 1-like isoform X1 [KO:K06279]
108700666  [KO:K04448]
108700774  erbb2.L; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
108701647  [KO:K19662] [EC:2.7.11.13]
108702159  prkca.S; protein kinase C alpha type isoform X3 [KO:K02677] [EC:2.7.11.13]
108702492  [KO:K05083] [EC:2.7.10.1]
108702812  [KO:K01116] [EC:3.1.4.11]
108703039  [KO:K05085] [EC:2.7.10.1]
108703204  [KO:K19662] [EC:2.7.11.13]
108703350  [KO:K05457]
108704012  raf1.L; RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
108704101  mapk10.S; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108704697  abl1.L; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
108705407  cbl.S; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
108706764  btc.S; probetacellulin isoform X1 [KO:K09783]
108706765  areg.S; amphiregulin isoform X1 [KO:K09782]
108706766  ereg.S; proepiregulin [KO:K09784]
108706826  [KO:K05455]
108706884  pik3r2.S; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
108706896  shc2.S; SHC-transforming protein 2 [KO:K17447]
108706999  [KO:K17448]
108708565  erbb3.L; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
108709342  crk.S; adapter molecule crk-like isoform X1 [KO:K04438]
108709405  cdkn1a.S; cyclin-dependent kinase inhibitor 1 [KO:K06625]
108709700  nck2.S; cytoplasmic protein NCK2 [KO:K19862]
108709833  erbb3.S; receptor tyrosine-protein kinase erbB-3 isoform X1 [KO:K05084] [EC:2.7.10.1]
108710179  egf.L; pro-epidermal growth factor [KO:K04357]
108710741  [KO:K06624]
108710907  hbegf.L; proheparin-binding EGF-like growth factor [KO:K08523]
108711056  btc.L; probetacellulin isoform X2 [KO:K09783]
108711064  areg.L; amphiregulin [KO:K09782]
108711073  ereg.L; proepiregulin [KO:K09784]
108711272  nrg4.L; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
108711398  shc4.L; SHC-transforming protein 4 [KO:K17449]
108711504  mapk10.L; mitogen-activated protein kinase 10 L homeolog isoform 1 [KO:K04440] [EC:2.7.11.24]
108712234  [KO:K05455]
108712318  shc4.S; SHC-transforming protein 4 [KO:K17449]
108712520  krasl.S; GTPase KRas isoform X1 [KO:K07827]
108712641  [KO:K04515] [EC:2.7.11.17]
108712658  map2k7.S; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
108712769  tgfa.S; protransforming growth factor alpha [KO:K08774]
108712802  map2k1.S; dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
108713027  pik3r2.L; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
108713169  shc2.L; SHC-transforming protein 2 [KO:K17447]
108713286  hbegf.S; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
108713905  [KO:K02158]
108714087  plcg2.L; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
108714850  [KO:K17448]
108715151  [KO:K02158]
108716398  pak5.L; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
108716660  sos1.L; son of sevenless homolog 1 [KO:K03099]
108717120  pik3cb.L; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
108717139  pak2.L; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
108717760  pak5.S; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
108717808  sos1.S; son of sevenless homolog 1 [KO:K03099]
108718090  pik3ca.S; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108718190  pik3cb.S; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108719445  [KO:K01116] [EC:3.1.4.11]
108719997  egfr.S; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
373647  src.S; tyrosine-protein kinase Src-1 [KO:K05704] [EC:2.7.10.2]
373752  pik3ca.L; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
373818  abl2.S; tyrosine-protein kinase ABL2 isoform X1 [KO:K08887] [EC:2.7.10.2]
378493  pak3.L; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
379050  jun.S; jun proto-oncogene S homeolog [KO:K04448]
379052  myc.S; transcriptional regulator Myc-A [KO:K04377]
379783  akt2.L; RAC-beta serine/threonine-protein kinase A [KO:K04456] [EC:2.7.11.1]
379876  mapk8.L; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
379991  map2k1.L; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
380430  src.L; tyrosine-protein kinase Src-2 [KO:K05704] [EC:2.7.10.2]
380508  camk2g.S; calcium/calmodulin dependent protein kinase (CaM kinase) II gamma S homeolog [KO:K04515] [EC:2.7.11.17]
394276  rps6kb1.S; ribosomal protein S6 kinase B1 S homeolog [KO:K04688] [EC:2.7.11.1]
394347  rps6kb1.L; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
394391  map2k7.L; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
397771  kras.L; kirsten rat sarcoma viral oncogene homolog L homeolog [KO:K07827]
397785  mapk1.L; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
397789  camk2b.L; calcium/calmodulin dependent protein kinase (CaM kinase) II beta L homeolog [KO:K04515] [EC:2.7.11.17]
397857  raf1.S; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
398126  pak1.S; p21-activated kinase 1 [KO:K04409] [EC:2.7.11.1]
398194  cbl.L; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:2.3.2.27]
398224  pak4.L; p21-activated kinase 4 [KO:K05734] [EC:2.7.11.1]
398359  plcg1.L; phospholipase C gamma 1 L homeolog [KO:K01116] [EC:3.1.4.11]
398360  plcg1.S; phospholipase C gamma 1 S homeolog [KO:K01116] [EC:3.1.4.11]
398376  camk2d.L; calcium/calmodulin-dependent protein kinase type II delta chain-like isoform X8 [KO:K04515] [EC:2.7.11.17]
398499  mapk8.S; mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
398782  MGC68680; uncharacterized protein LOC398782 [KO:K04409] [EC:2.7.11.1]
398861  nck2.L; NCK adaptor protein 2 L homeolog [KO:K19862]
398892  araf.L; A-Raf proto-oncogene, serine/threonine kinase L homeolog [KO:K08845] [EC:2.7.11.1]
398951  crk.L; adapter molecule crk [KO:K04438]
398973  braf.S; B-Raf [KO:K04365] [EC:2.7.11.1]
398985  mapk1.S; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
399056  araf.S; A-Raf proto-oncogene, serine/threonine kinase S homeolog [KO:K08845] [EC:2.7.11.1]
399090  pak2.S; p21-activated kinase 2 [KO:K04410] [EC:2.7.11.1]
399097  gsk3b.L; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
399160  camk2d.S; calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:2.7.11.17]
399170  akt1.S; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
399176  stat5b.L; signal transducer and activator of transcription 5B L homeolog [KO:K11224]
399198  shc1.L; SHC-transforming protein 1 [KO:K06279]
399202  pik3r1.S; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
399284  camk2a.S; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
399286  ptk2.L; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
399308  nck1.L; NCK adaptor protein 1 L homeolog [KO:K07365]
399315  myc.L; transcriptional regulator Myc-B [KO:K04377]
399400  jun.L; jun proto-oncogene L homeolog [KO:K04448]
399406  hras.L; Harvey rat sarcoma viral oncogene homolog L homeolog [KO:K02833]
399446  nras.L; GTPase NRas [KO:K07828]
399458  grb2.L; growth factor receptor-bound protein 2-A [KO:K04364]
399471  map2k4.L; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04430] [EC:2.7.12.2]
403362  abl2.L; uncharacterized protein LOC403362 [KO:K08887] [EC:2.7.10.2]
414569  crkl.S; uncharacterized protein LOC414569 [KO:K04438]
414637  stat5b.S; signal transducer and activator of transcription 5B S homeolog [KO:K11224]
431829  cblb.S; E3 ubiquitin-protein ligase CBL-B-B [KO:K22517] [EC:2.3.2.27]
431908  map2k4.S; dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04430] [EC:2.7.12.2]
432072  ptk2.S; uncharacterized protein LOC432072 [KO:K05725] [EC:2.7.10.2]
432172  akt2.S; RAC-beta serine/threonine-protein kinase B [KO:K04456] [EC:2.7.11.1]
443854  cblb.L; E3 ubiquitin-protein ligase CBL-B-A [KO:K22517] [EC:2.3.2.27]
443964  pik3r1.L; phosphoinositide-3-kinase regulatory subunit 1 L homeolog [KO:K02649]
444095  grb2.S; growth factor receptor-bound protein 2-B [KO:K04364]
446786  pik3r3.S; phosphoinositide-3-kinase regulatory subunit 3 S homeolog [KO:K02649]
447031  prkca.L; protein kinase C, alpha L homeolog [KO:K02677] [EC:2.7.11.13]
447268  braf.L; B-Raf proto-oncogene, serine/threonine kinase L homeolog [KO:K04365] [EC:2.7.11.1]
447419  crkl.L; v-crk avian sarcoma virus CT10 oncogene homolog-like L homeolog [KO:K04438]
447594  pik3r3.L; phosphoinositide-3-kinase regulatory subunit 3 L homeolog [KO:K02649]
492305  cdkn1a.L; cyclin-dependent kinase inhibitor 1 [KO:K06625]
492306  cdkn1b.S; cyclin-dependent kinase inhibitor 1B (p27, Kip1) S homeolog [KO:K06624]
496037  tgfa.L; transforming growth factor alpha L homeolog precursor [KO:K08774]
724070  erbb4.L; erb-b2 receptor tyrosine kinase 4 L homeolog precursor [KO:K05085] [EC:2.7.10.1]
724072  egfr.L; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
734245  gab1.L; uncharacterized protein LOC734245 [KO:K09593]
734248  gab1.S; GRB2 associated binding protein 1 S homeolog [KO:K09593]
779056  [KO:K03083] [EC:2.7.11.26]
779200  nck1.S; NCK adaptor protein 1 S homeolog [KO:K07365]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:14967450
  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
PMID:11252954
  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
PMID:16829981
  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
PMID:17000658
  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
PMID:16377102
  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
PMID:14744244
  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
PMID:12851486
  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
PMID:15864276
  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
PMID:16729045
  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
PMID:16729043
  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
PMID:10880430
  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
Bioessays 20:913-21 (1998)
DOI:10.1002/(SICI)1521-1878(199811)20:11<913::AID-BIES6>3.0.CO;2-T
Reference
PMID:15863494
  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
PMID:10490623
  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
xla04010  MAPK signaling pathway
xla04020  Calcium signaling pathway
xla04110  Cell cycle
xla04150  mTOR signaling pathway
KO pathway
ko04012   

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