MULTIPLE COMPONENTS OF THE B-CELL ANTIGEN RECEPTOR COMPLEX ASSOCIATE WITH THE PROTEIN-TYROSINE-PHOSPHATASE, CD45

Signal transduction via the B cell antigen receptor complex is regulat ed by changes in tyrosine phosphorylation of several proteins. The equ ilibrium between tyrosine phosphorylation and dephosphorylation is reg ulated by the combined action of protein tyrosine kinase and protein t yrosine phosphatase enzymes. In particular, the protein tyrosine phosp hatase, CD45, has been shown to play an essential role in signal trans duction via the B cell antigen receptor. Therefore, experiments were p erformed to examine the intermolecular associations between CD45 and p hosphotyrosine containing proteins in the B cell to identify potential substrates for CD45. Based on coprecipitation experiments, CD45 was f ound to be physically associated with multiple components of the B cel l antigen receptor complex including the MB-1/B29 heterodimer. Additio nally, CD45 was selectively associated with the src family protein tyr osine kinase, lyn. Neither blk nor fyn, were observed to interact with CD45 even though they have been implicated in antigen receptor signal transduction. This finding suggests that CD45 may preferentially regu late the phosphorylation of lyn and thus, its activity. In summary, th ese studies provide evidence to support the hypothesis that CD45 regul ates antigen receptor-mediated signal transduction by controlling the tyrosine phosphorylation of multiple components of the antigen recepto r complex.