PTPN12 dephosphorylates EGFR at Y1172 (Y1148)

Stable Identifier
R-HSA-8864029
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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PTPN12 dephosphorylates EGFR at Y1172 (Y1148)
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PTPN12 protein tyrosine phosphatase dephosphorylates activated EGFR at tyrosine residue Y1148 (Y1148 corresponds to Y1172 in the nascent EGFR sequence which includes the 24 amino acid long signal peptide at the N-terminus). PTPN12-mediated dephosphorylation of activated EGFR inhibits SHC1 recruitment to the p-Y1148 (i.e. p-Y1172) docking site, thus attenuating downstream RAS activation (Sun et al. 2011). The recruitment of SHC1 to p-Y1148 (i.e. Y1172) of EGFR is mediated by the N-terminal phosphotyrosine interaction domain (PID) of SHC1 (Batzer et al. 1995, Songyang et al. 1995).
Literature References
PubMed ID Title Journal Year
7542744 The phosphotyrosine interaction domain of Shc binds an LXNPXY motif on the epidermal growth factor receptor

Schlessinger, J, Batzer, AG, Blaikie, P, Nelson, K, Margolis, B

Mol. Cell. Biol. 1995
21376233 Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase

Schmitt, E, Creighton, CJ, Hilsenbeck, SG, Gygi, SP, Bernardi, RJ, Osborne, CK, Westbrook, TF, Muzny, D, Kessler, JD, Shaw, CA, Pavlova, NN, Schiff, R, Hu, G, Sun, T, Elledge, SJ, Zhou, C, Bentires-Alj, M, Wheeler, DA, Dephoure, N, Huang, J, Li, MZ, Gibbs, RA, Rao, M, Nguyen, DX, Aceto, N, Meerbrey, KL, Migliaccio, I, Botero, M

Cell 2011
7541030 The phosphotyrosine interaction domain of SHC recognizes tyrosine-phosphorylated NPXY motif

Cantley, LC, Songyang, Z, Shoelson, SE, Chaudhuri, M, Margolis, B

J. Biol. Chem. 1995
Participants
Input
Output
Participates
as an event of
Event Information
Go Biological Process
negative regulation of ERBB signaling pathway (1901185)
Catalyst Activity

protein tyrosine phosphatase activity of PTPN12 [cytosol]

Physical Entity
PTPN12 [cytosol] (Homo sapiens)
Activity
protein tyrosine phosphatase activity (GO:0004725)
Orthologous Events
PTPN12 dephosphorylates EGFR at Y1172 (Y1148) (Canis familiaris)
PTPN12 dephosphorylates EGFR at Y1172 (Y1148) (Gallus gallus)
PTPN12 dephosphorylates EGFR at Y1172 (Y1148) (Mus musculus)
PTPN12 dephosphorylates EGFR at Y1172 (Y1148) (Rattus norvegicus)
PTPN12 dephosphorylates EGFR at Y1172 (Y1148) (Sus scrofa)
PTPN12 dephosphorylates EGFR at Y1172 (Y1148) (Xenopus tropicalis)
Authored
Orlic-Milacic, M  (2016-03-11)
Reviewed
Ayoub, E  (2016-08-04)
Tremblay, M  (2016-08-04)
Created
Orlic-Milacic, M  (2016-03-11)
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