Meta-Biol

• Pathways

PTPN12 protein tyrosine phosphatase dephosphorylates activated ERBB2 at tyrosine residue Y1248 and activated EGFR at tyrosine residue Y1148 (Y1148 corresponds to Y1172 of the nascent EGFR, with 24 amino acid signal peptide at the N-terminus). PTPN12-mediated dephosphorylation of ERBB2 attenuates downstream RAS activation, as Y1248 is involved in SHC1 recruitment. Similar to Y1148 of EGFR, Y1248 of ERBB2 is part of the NPXY motif that is, when phosphorylated on the tyrosine residue, recognized by the N-terminal phosphotyrosine interaction domain (PID) of SHC1 (Batzer et al. 1995, Songyang et al. 1995). SHC1 itself could be a target for PTPN12. PTPN12 function is frequently lost in triple negative breast cancer (Sun et al. 2011).