COCLUSTERING CD45 WITH CD4 OR CD8 ALTERS THE PHOSPHORYLATION AND KINASE-ACTIVITY OF P56LCK

Antibody-mediated CD4 crosslinking results in increased tyrosine phosphorylation and tyrosine kinase activity of the associated p56kk. Treatment with anti-CD4 and anti-Ig also induced the phosphorylation of p56kk in a CD45− mutant 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 p56kk 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. © 1990, Rockefeller University Press., All rights reserved.