LPAP, A NOVEL 32-KDA PHOSPHOPROTEIN THAT INTERACTS WITH CD45 IN HUMAN-LYMPHOCYTES

CD45, a leukocyte-specific protein tyrosine phosphatase involved in si gnal transduction, has previously been shown to associate with a 32-kD a phosphoprotein in human T-lymphocytes and T-lymphoma cell lines. The 32-kDa protein was purified and its coding cDNA cloned. Since express ion of the protein was found to be restricted to B- and T-lymphocytes it was termed LPAP (lymphocyte phosphatase-associated phosphoprotein). LPAP exists in two differentially phosphorylated forms in resting hum an T-lymphocytes c, both of which undergo alterations during T-lymphoc yte activation. Analysis of LPAP protein and mRNA expression in CD45-d eficient mutant T-cell lines suggests that LPAP protein is subjected t o degradation in the absence of its binding partner, CD45. Stable expr ession of LPAP protein seems to require particular portions of CD45 di stinct from the phosphatase domains. In pervanadate-treated human T-ly mphocytes LPAP undergoes phosphorylation on tyrosine residues in vivo. Since tyrosine phosphorylation of LPAP is undetectable in T-lymphocyt es expressing enzymatically active CD45, these data suggest that LPAP likely represents a novel substrate for CD45.