KEGG   PATHWAY: tup04012
Entry
tup04012                    Pathway                                
Name
ErbB signaling pathway - Tupaia chinensis (Chinese tree shrew)
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
tup04012  ErbB signaling pathway
tup04012

Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102468023  ERBB3; erb-b2 receptor tyrosine kinase 3 [KO:K05084] [EC:2.7.10.1]
102468951  BTC; betacellulin [KO:K09783]
102469271  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102469580  CBL; Cbl proto-oncogene [KO:K04707] [EC:2.3.2.27]
102469651  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102470554  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102472173  PAK2; p21 (RAC1) activated kinase 2 [KO:K04410] [EC:2.7.11.1]
102472233  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102472295  SHC3; SHC adaptor protein 3 [KO:K17448]
102472689  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
102473890  NRG4; neuregulin 4 [KO:K05458]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102474805  PAK5; p21 (RAC1) activated kinase 5 [KO:K05736] [EC:2.7.11.1]
102475423  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
102475723  EREG; epiregulin [KO:K09784]
102475730  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102476038  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102476130  AREG; amphiregulin [KO:K09782]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102477086  ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO:K08887] [EC:2.7.10.2]
102477222  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102477389  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102479734  SHC4; SHC adaptor protein 4 [KO:K17449]
102480748  NRG2; neuregulin 2 [KO:K05456]
102481002  SHC1; SHC adaptor protein 1 [KO:K06279]
102481444  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
102481863  SHC2; SHC adaptor protein 2 [KO:K17447]
102481881  NRG3; neuregulin 3 [KO:K05457]
102482008  ERBB4; erb-b2 receptor tyrosine kinase 4 [KO:K05085] [EC:2.7.10.1]
102482865  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
102482912  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102483369  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
102483700  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102483786  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102485262  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102485272  CBLB; Cbl proto-oncogene B [KO:K22517] [EC:2.3.2.27]
102485304  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102486599  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
102487164  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
102490159  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102490423  EGF; epidermal growth factor [KO:K04357]
102491807  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102492323  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102493080  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102493152  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
102493230  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102493239  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
102493316  PAK6; p21 (RAC1) activated kinase 6 [KO:K05735] [EC:2.7.11.1]
102493856  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
102494625  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102494629  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102494657  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
102494763  ELK1; ELK1, ETS transcription factor [KO:K04375]
102495430  PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
102495954  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102496534  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102496748  NCK1; NCK adaptor protein 1 [KO:K07365]
102496870  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102497095  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102497204  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102497440  NCK2; NCK adaptor protein 2 [KO:K19862]
102497468  GAB1; GRB2 associated binding protein 1 [KO:K09593]
102497488  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102497681  NRG1; neuregulin 1 [KO:K05455]
102497817  TGFA; transforming growth factor alpha [KO:K08774]
102498069  BAD; BCL2 associated agonist of cell death [KO:K02158]
102498262  HBEGF; heparin binding EGF like growth factor [KO:K08523]
102499692  PAK4; p21 (RAC1) activated kinase 4 [KO:K05734] [EC:2.7.11.1]
102500036  PAK3; p21 (RAC1) activated kinase 3 [KO:K05733] [EC:2.7.11.1]
102500069  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102500732  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102501235  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
102501999  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102503259  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
106736453  [KO:K00922] [EC:2.7.1.153]
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
tup04010  MAPK signaling pathway
tup04020  Calcium signaling pathway
tup04110  Cell cycle
tup04150  mTOR signaling pathway
tup04151  PI3K-Akt signaling pathway
tup05212  Pancreatic cancer
tup05213  Endometrial cancer
tup05214  Glioma
tup05223  Non-small cell lung cancer
KO pathway
ko04012   

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