KEGG   PATHWAY: ssc04012
ssc04012                    Pathway                                

ErbB signaling pathway - Sus scrofa (pig)
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.
Environmental Information Processing; Signal transduction
Pathway map
ssc04012  ErbB signaling pathway

Sus scrofa (pig) [GN:ssc]
397083  EGF; pro-epidermal growth factor precursor [KO:K04357]
397484  TGFA; protransforming growth factor alpha precursor [KO:K08774]
397668  AREG; amphiregulin precursor [KO:K09782]
397070  EGFR; epidermal growth factor receptor precursor [KO:K04361] [EC:]
100516641  ERBB2; receptor tyrosine-protein kinase erbB-2 precursor [KO:K05083] [EC:]
100152497  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:]
100518663  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:]
397674  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:]
397394  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:]
100626014  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X7 [KO:K04515] [EC:]
100516166  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:]
397184  PRKCA; LOW QUALITY PROTEIN: protein kinase C alpha type [KO:K02677] [EC:]
100522792  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:]
100518074  PRKCG; protein kinase C gamma type isoform X3 [KO:K19663] [EC:]
100518854  CBL; E3 ubiquitin-protein ligase CBL isoform X1 [KO:K04707] [EC:]
100621690  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:]
397550  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
397340  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
100154503  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:]
102167153  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:]
100192444  CRK; adapter molecule crk [KO:K04438]
100525363  CRKL; crk-like protein [KO:K04438]
100524544  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:]
100627019  ABL2; Abelson tyrosine-protein kinase 2 isoform X6 [KO:K08887] [EC:]
100192438  NCK1; cytoplasmic protein NCK1 [KO:K07365]
100192439  NCK2; cytoplasmic protein NCK2 [KO:K19862]
100525766  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:]
100511837  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:]
100624533  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:]
100627936  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:]
100152316  PAK5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:]
100153981  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:]
100520100  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X2 [KO:K04430] [EC:]
100520418  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X5 [KO:K04431] [EC:]
396610  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
100521736  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:]
396609  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:]
396913  JUN; transcription factor AP-1 [KO:K04448]
100522002  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
100505411  BTC; probetacellulin isoform X10 [KO:K09783]
397564  HBEGF; proheparin-binding EGF-like growth factor precursor [KO:K08523]
100620969  EREG; proepiregulin [KO:K09784]
100525045  ERBB3; receptor tyrosine-protein kinase erbB-3 [KO:K05084] [EC:]
102164569  NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455]
100625643  NRG2; pro-neuregulin-2, membrane-bound isoform [KO:K05456]
100525789  ERBB4; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-4 [KO:K05085] [EC:]
100156321  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
110259382  SHC2; SHC-transforming protein 2 [KO:K17447]
102164918  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
100526147  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
100192436  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100156602  SOS2; son of sevenless homolog 2 [KO:K03099]
100520187  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
110259208  HRAS; GTPase HRas isoform X1 [KO:K02833]
100518251  KRAS; GTPase KRas isoform X2 [KO:K07827]
100739349  NRAS; GTPase NRas precursor [KO:K07828]
397601  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:]
100514612  BRAF; serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:]
100737448  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
100233191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
100525505  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
100153927  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
445013  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
448810  MYC; myc proto-oncogene protein [KO:K04377]
100511026  GAB1; LOW QUALITY PROTEIN: GRB2-associated-binding protein 1 [KO:K09593]
100158106  NRG3; LOW QUALITY PROTEIN: pro-neuregulin-3, membrane-bound isoform [KO:K05457]
100516621  NRG4; pro-neuregulin-4, membrane-bound isoform isoform X2 [KO:K05458]
100518131  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:]
100621789  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
100622559  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:]
100511937  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100739510  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100623707  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100126861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
100513811  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
100127478  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
100127359  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:]
100127158  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:]
100512153  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:]
100627508  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
100521065  BAD; LOW QUALITY PROTEIN: bcl2-associated agonist of cell death [KO:K02158]
100126852  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:]
397584  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100152215  CDKN1A; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1 [KO:K06625]
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Marmor MD, Skaria KB, Yarden Y.
Signal transduction and oncogenesis by ErbB/HER receptors.
Int J Radiat Oncol Biol Phys 58:903-13 (2004)
Yarden Y, Sliwkowski MX.
Untangling the ErbB signalling network.
Nat Rev Mol Cell Biol 2:127-37 (2001)
Citri A, Yarden Y.
EGF-ERBB signalling: towards the systems level.
Nat Rev Mol Cell Biol 7:505-16 (2006)
Scaltriti M, Baselga J.
The epidermal growth factor receptor pathway: a model for targeted therapy.
Clin Cancer Res 12:5268-72 (2006)
Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS.
Epidermal growth factor receptor (EGFR) signaling in cancer.
Gene 366:2-16 (2006)
Holbro T, Hynes NE.
ErbB receptors: directing key signaling networks throughout life.
Annu Rev Pharmacol Toxicol 44:195-217 (2004)
Liang J, Slingerland JM.
Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.
Cell Cycle 2:339-45 (2003)
Hynes NE, Lane HA.
ERBB receptors and cancer: the complexity of targeted inhibitors.
Nat Rev Cancer 5:341-54 (2005)
Oda K, Matsuoka Y, Funahashi A, Kitano H.
A comprehensive pathway map of epidermal growth factor receptor signaling.
Mol Syst Biol 1:2005.0010 (2005)
Schulze WX, Deng L, Mann M.
Phosphotyrosine interactome of the ErbB-receptor kinase family.
Mol Syst Biol 1:2005.0008 (2005)
Olayioye MA, Neve RM, Lane HA, Hynes NE.
The ErbB signaling network: receptor heterodimerization in development and cancer.
EMBO J 19:3159-67 (2000)
McCarty JH.
The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events.
Clark DE, Williams CC, Duplessis TT, Moring KL, Notwick AR, Long W, Lane WS, Beuvink I, Hynes NE, Jones FE.
ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.
J Biol Chem 280:24175-80 (2005)
Muthuswamy SK, Gilman M, Brugge JS.
Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.
Mol Cell Biol 19:6845-57 (1999)
Hashimoto Y, Katayama H, Kiyokawa E, Ota S, Kurata T, Gotoh N, Otsuka N, Shibata M, Matsuda M.
Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.
J Biol Chem 273:17186-91 (1998)
ssc04010  MAPK signaling pathway
ssc04020  Calcium signaling pathway
ssc04110  Cell cycle
ssc04150  mTOR signaling pathway
ssc04151  PI3K-Akt signaling pathway
ssc05212  Pancreatic cancer
ssc05213  Endometrial cancer
ssc05214  Glioma
ssc05223  Non-small cell lung cancer
KO pathway

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