The low Mr phosphotyrosine protein phosphatase behaves differently when phosphorylated at Tyr131 or Tyr132 by Src kinase

The low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) is phosphorylated 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 in vitro the enzyme at two tyrosine residues, Tyr(131) and Tyr(132), previously indicated as the main phosphorylation Bites of the enzyme, whereas phosphorylation by the PDGF-R kinase is much less effective and not specific. The effects of LMW-PTP phosphorylation at each tyrosine residue were investigated by using Tyr(131) and Tyr(132) mutants. We found that the phosphorylation at either residue has differing effects on the enzyme behaviour: Tyr(131) phosphorylation is followed by a strong (about 25-fold) increase of the enzyme specific activity, whereas phosphorylation at Tyr(132) leads to Grb2 recruitment. These differing effects are discussed on the light of the enzyme structure. (C) 1999 Federation of European Biochemical Societies.