CD45 REGULATION OF TYROSINE PHOSPHORYLATION AND ENZYME-ACTIVITY OF SRC FAMILY KINASES

Previous analyses have suggested that the CD45 tyrosine phosphatase ac tivates src family tyrosine kinases p56(lck) and p59(fyn) by dephospho rylating regulatory COOH-terminal residues. We have examined the statu s of p56(lck) and p59(fyn) in murine and human CD45(-) T cell lines. S urprisingly, despite the fact that p56(lck) and p59(fyn) were spontane ously hyperphosphorylated, the tyrosine kinase activity of both enzyme s was increased in CD45(-) versus CD45(+) cells. In vitro exposure of hyperphosphorylated p56(lck) to CD45 decreased enzyme activity to near -basal levels. Lck from CD45(-) cells was hyperphosphorylated on the c yanogen bromide digestion fragment that contains the negative regulato ry residue Tyr-505, and the identity of this site of phosphorylation w as confirmed by trypsin digestion followed by high performance liquid chromatography. Loss of CD45 results, therefore, in a paradoxical hype rphosphorylation of the COOH-terminal tyrosine and increased src famil y kinase enzymatic activity.