Site-Specific Incorporation of a Phosphotyrosine Mimetic Reveals a Role for Tyrosine Phosphorylation of SHP-2 in Cell Signaling

摘要: Abstract The regulation of protein tyrosine phosphatase (PTPase) SHP-2 is proposed to involve phosphorylation on two tail residues. Using "expressed ligation", nonhydrolyzable phosphotyrosine analogs were introduced at known sites in SHP-2. Biochemical analysis suggests that a phosphonate Tyr542 interacts intramolecularly with the N-terminal SH2 domain relieve basal inhibition PTPase, whereas Tyr-580 stimulates PTPase activity by interaction C-terminal domain. Microinjection experiments indicate single Tyr-542 sufficient activate MAP kinase pathway living cells. These studies support novel mechanism explaining how important signal transduction.