DISRUPTION OF LYMPHOCYTE FUNCTION AND SIGNALING IN CD45-ASSOCIATED PROTEIN-NULL MICE

CD45-AP specifically associates with CD45, a protein tyrosine phosphat ase essential for lymphocyte differentiation and antigen receptor-medi ated signal transduction. CD45 is thought to mediate antigen receptor signaling by dephosphorylating regulatory tyrosine residues on Src fam ily protein tyrosine kinases such as Lck. However, the mechanism for r egulating CD45 protein tyrosine phosphatase activity remains unclear. CD45-AP-null mice were created to examine the role of CD45-AP in CD45- mediated signal transduction. T and B lymphocytes showed reduced proli feration in response to antigen receptor stimulation. Both mixed leuko cyte reaction and cytotoxic T lymphocyte functions of T cells were als o markedly decreased in CD45-AP-null mice. Interestingly, the interact ion between CD45 and Lck was significantly reduced in CD45-AP-null T c ells, indicating that CD45-AP directly or indirectly mediates the inte raction of CD45 with Lck. Our data indicate that CD45-AP is required f or normal antigen receptor signaling and function in lymphocytes.