KEGG   PATHWAY: cjc04012
Entry
cjc04012                    Pathway                                

Name
ErbB signaling pathway - Callithrix jacchus (white-tufted-ear marmoset)
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
cjc04012  ErbB signaling pathway
cjc04012

Organism
Callithrix jacchus (white-tufted-ear marmoset) [GN:cjc]
Gene
100388651  EGF; epidermal growth factor [KO:K04357]
100402888  TGFA; transforming growth factor alpha [KO:K08774]
100387931  AREG; amphiregulin [KO:K09782]
100412158  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100391332  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
100397497  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
100390347  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
100397956  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
100405903  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
100391424  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
100390938  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
100410352  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
100391814  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
100410136  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
100404028  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
100408313  CBL; Cbl proto-oncogene [KO:K04707] [EC:2.3.2.27]
100409801  CBLB; Cbl proto-oncogene B [KO:K22517] [EC:2.3.2.27]
100388917  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
100388552  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
100386165  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
100395283  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
100390206  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
100399916  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
100398414  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
100388523  ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO:K08887] [EC:2.7.10.2]
100395287  NCK1; NCK adaptor protein 1 [KO:K07365]
100401429  NCK2; NCK adaptor protein 2 [KO:K19862]
100392970  PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
100405552  PAK2; p21 (RAC1) activated kinase 2 [KO:K04410] [EC:2.7.11.1]
100413676  PAK3; p21 (RAC1) activated kinase 3 [KO:K05733] [EC:2.7.11.1]
100394713  PAK4; p21 (RAC1) activated kinase 4 [KO:K05734] [EC:2.7.11.1]
100411048  PAK5; p21 (RAC1) activated kinase 5 [KO:K05736] [EC:2.7.11.1]
100387874  PAK6; p21 (RAC1) activated kinase 6 [KO:K05735] [EC:2.7.11.1]
100386168  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
100412930  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
100392721  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100387686  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100390109  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100400411  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
100393766  ELK1; ELK1, ETS transcription factor [KO:K04375]
100387579  BTC; betacellulin [KO:K09783]
100392997  HBEGF; heparin binding EGF like growth factor [KO:K08523]
100399761  EREG; epiregulin [KO:K09784]
100409758  ERBB3; erb-b2 receptor tyrosine kinase 3 [KO:K05084] [EC:2.7.10.1]
100409658  NRG1; neuregulin 1 [KO:K05455]
100391893  NRG2; neuregulin 2 [KO:K05456]
100402965  ERBB4; erb-b2 receptor tyrosine kinase 4 [KO:K05085] [EC:2.7.10.1]
100390337  SHC1; SHC adaptor protein 1 [KO:K06279]
100415083  SHC2; SHC adaptor protein 2 [KO:K17447]
100402406  SHC3; SHC adaptor protein 3 [KO:K17448]
100392220  SHC4; SHC adaptor protein 4 [KO:K17449]
100395682  GRB2; growth factor receptor bound protein 2 [KO:K04364]
100414931  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
100410124  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
100406017  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
100414782  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100387961  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
100403091  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
100415300  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100387394  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100393991  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100400700  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100404815  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100407754  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
100406544  GAB1; GRB2 associated binding protein 1 [KO:K09593]
100387417  NRG3; neuregulin 3 [KO:K05457]
100410240  NRG4; neuregulin 4 [KO:K05458]
100403494  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
100391655  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
100398849  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
100406689  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
100392639  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
100414659  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
100404447  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
100399039  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
100388080  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
100406608  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
100397180  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
100409247  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
100386453  EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205]
100412880  BAD; BCL2 associated agonist of cell death [KO:K02158]
100387683  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100387508  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
100894215  CDKN1A; cyclin dependent kinase inhibitor 1A [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
cjc04010  MAPK signaling pathway
cjc04020  Calcium signaling pathway
cjc04110  Cell cycle
cjc04150  mTOR signaling pathway
cjc04151  PI3K-Akt signaling pathway
cjc05212  Pancreatic cancer
cjc05213  Endometrial cancer
cjc05214  Glioma
cjc05223  Non-small cell lung cancer
KO pathway
ko04012   
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