PP60(V-SRC) PHOSPHORYLATES AND ACTIVATES LOW-MOLECULAR-WEIGHT PHOSPHOTYROSINE-PROTEIN PHOSPHATASE

Low M(r) phosphotyrosine-protein phosphatase belongs to the non-recept or cytosolic phosphotyrosine-protein phosphatase subfamily. It has bee n demonstrated that this enzyme dephosphorylates receptor tyrosine kin ases, namely the epidermal growth factor receptor in vitro and the pla telet-derived growth factor receptor in vivo. Low M(r) phosphotyrosine -protein phosphatase is constitutively tyrosine-phosphorylated in NIH/ 3T3 cells transformed by pp60(v-src). The same tyrosine kinase, previo usly immunoprecipitated, phosphorylates this enzyme in vitro as well. Phosphorylation is enhanced using phosphatase inhibitors and phenylars ine oxide-inactivated phosphatase, consistently with the existence of an auto-dephosphorylation process. Intermolecular dephosphorylation is demonstrated adding the active enzyme in a solution containing the in activated and previously phosphorylated one. This tyrosine phosphoryla tion correlates with an increase in catalytic activity. Our results pr ovide evidence of a physiological mechanism of low M(r) phosphotyrosin e-protein phosphatase activity regulation.