REGULATION OF THE LOW-MOLECULAR-WEIGHT PHOSPHOTYROSINE PHOSPHATASE BYPHOSPHORYLATION AT TYROSINE-131 AND TYROSINE-132

Activation of resting T lymphocytes is initiated by rapid but transien t tyrosine phosphorylation of a number of cellular proteins, Several p rotein tyrosine kinases and protein tyrosine phosphatases are known to be important for this response, Here we report that normal T lymphocy tes express the B isoform of low molecular weight protein tyrosine pho sphatase B (LMPTP-B), The cDNA was cloned from Jurkat T cells, and an antiserum was raised against it, LMPTP immunoprecipitated from resting Jurkat T cells was found to be tyrosine phosphorylated. On stimulatio n of the cells through their T cell antigen receptor, the phosphotyros ine content of LMPTP-B declined rapidly. In co-transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP, whereas Csk, Zap, and Jak 2 did not. Most of the phosphate was located at Tyr-131, and some was also located at Tyr-132. Incubation of wild-type LMPTP with Lck and ad enosine 5'-O-(thiotriphosphate) caused a 2-fold increase in the activi ty of LMPTP, Site-directed mutagenesis showed that Tyr-131 is importan t for the catalytic activity of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr-132, is responsible for the activ ation.