Coclustering CD 45 with CD 4 or CD 8 Alters the Phosphorylation and Kinase Activity of p 56 "

Antibody-mediated CD4 crosslinking results in increased tyrosine phosphorylation and tyrosine kinase activity of the associated p56" . Treatment with anti-CD4 and anti-Ig also induced the phosphorylation of p56kk in a CD45mutant cell line, indicating that the increase in phosphotyrosine content of p56kk is not the result of being sequestered from CD45 protein tyrosine phosphatase (PTPase) . Antibody-mediated coclustering of CD45 with CD4 inhibited the anti-CD4-induced phosphorylation of p56" on tyrosine and the concomitant increase in in vitro kinase activity. Similar results were obtained when CD45 was coclustered with CD8 on cytotoxic T cell lines. These observations provide strong evidence that p56kk is a substrate for CD45 in vivo and provide an assay to study the regulation and specificity ofCD45 PTPase activity.