KEGG   PATHWAY: lav04012
Entry
lav04012                    Pathway                                

Name
ErbB signaling pathway - Loxodonta africana (African savanna elephant)
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
lav04012  ErbB signaling pathway
lav04012

Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100670137  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
100665332  TGFA; protransforming growth factor alpha [KO:K08774]
100661838  AREG; amphiregulin [KO:K09782]
100659125  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
100662583  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X2 [KO:K05083] [EC:2.7.10.1]
100677739  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
100658990  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
104846071  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
100653927  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100663321  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
100658516  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
100665537  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100672078  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
100671733  PRKCG; LOW QUALITY PROTEIN: protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100658892  CBL; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
100669603  CBLB; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
100672448  signal transducer and activator of transcription 5A [KO:K11223]
100669299  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
100675475  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
100668436  PTK2; LOW QUALITY PROTEIN: focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
100659273  CRK; adapter molecule crk isoform X1 [KO:K04438]
100662046  CRKL; crk-like protein [KO:K04438]
100677152  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100676988  ABL2; Abelson tyrosine-protein kinase 2 isoform X4 [KO:K08887] [EC:2.7.10.2]
100666870  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
100660400  NCK2; cytoplasmic protein NCK2 [KO:K19862]
100668003  LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 1-like [KO:K04409] [EC:2.7.11.1]
100664379  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
100668837  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
100661100  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
100666744  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
100660904  serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
100655007  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
100673238  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
100654943  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100674229  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100673395  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100670432  JUN; transcription factor AP-1 [KO:K04448]
100670835  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
100661273  BTC; probetacellulin [KO:K09783]
100675899  HBEGF; proheparin-binding EGF-like growth factor isoform X2 [KO:K08523]
100662121  EREG; proepiregulin [KO:K09784]
100668973  ERBB3; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:2.7.10.1]
100668360  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
100670957  NRG2; LOW QUALITY PROTEIN: pro-neuregulin-2, membrane-bound isoform [KO:K05456]
100656755  ERBB4; receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:2.7.10.1]
100653766  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
100659669  SHC3; SHC-transforming protein 3 [KO:K17448]
100654827  SHC4; SHC-transforming protein 4 [KO:K17449]
100655474  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100657379  SOS1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
100656200  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100661512  KRAS; GTPase KRas isoform X2 [KO:K07827]
100659051  NRAS; GTPase NRas [KO:K07828]
100671404  ARAF; serine/threonine-protein kinase A-Raf isoform X3 [KO:K08845] [EC:2.7.11.1]
100664119  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
100655727  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100667623  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100657587  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100658240  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100665157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100665874  MYC; myc proto-oncogene protein [KO:K04377]
100669213  GAB1; GRB2-associated-binding protein 1 isoform X2 [KO:K09593]
100664296  NRG3; LOW QUALITY PROTEIN: pro-neuregulin-3, membrane-bound isoform [KO:K05457]
100673971  NRG4; pro-neuregulin-4, membrane-bound isoform [KO:K05458]
100657948  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100658340  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100666266  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100653731  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100665045  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100675496  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100663184  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100657536  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100660187  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100660112  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100653946  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100671034  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100665518  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100668387  BAD; bcl2-associated agonist of cell death [KO:K02158]
100675105  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100674125  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100671706  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
lav04010  MAPK signaling pathway
lav04020  Calcium signaling pathway
lav04110  Cell cycle
lav04150  mTOR signaling pathway
lav04151  PI3K-Akt signaling pathway
lav05212  Pancreatic cancer
lav05213  Endometrial cancer
lav05214  Glioma
lav05223  Non-small cell lung cancer
KO pathway
ko04012   
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