The low M-r phosphotyrosine protein phosphatase behaves differently when phosphorylated at Tyr(131) or Tyr(132) by Src kinase

The low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) is p hosphorylated by Src and Src-related kinases both in vitro and in vivo; in Jurkat cells, and in NIH-3T3 cells, it becomes tyrosine-phosphorylated upon stimulation by PDGF, In this study we show that pp60(Src) phosphorylates i n vitro the enzyme at two tyrosine residues, Tyr(131) and Tyr(132), previou sly indicated as the main phosphorylation Bites of the enzyme, whereas phos phorylation by the PDGF-R kinase is much less effective and not specific. T he effects of LMW-PTP phosphorylation at each tyrosine residue were investi gated by using Tyr(131) and Tyr(132) mutants. We found that the phosphoryla tion at either residue has differing effects on the enzyme behaviour: Tyr(1 31) phosphorylation is followed by a strong (about 25-fold) increase of the enzyme specific activity, whereas phosphorylation at Tyr(132) leads to Grb 2 recruitment. These differing effects are discussed on the light of the en zyme structure. (C) 1999 Federation of European Biochemical Societies.