T-CELL ACTIVATION BY CLUSTERED TYROSINE KINASES

Many cellular recognition events in the immune system are initiated by aggregation of cell surface receptors that lack intrinsic protein-tyr osine kinase activity. Receptor-associated kinases related to the src proto-oncogene product have been found to be essential for cellular ac tivation and may interact with the cytoplasmic domains of the antigen receptor chains. We show here that anti-CD16 antibody-mediated cluster ing of chimeric transmembrane proteins bearing a CD16 extracellular do main and a Src family kinase intracellular domain is not sufficient to initiate a cellular activation signal in T cells, whereas clustering of similar chimeras bearing Syk or ZAP-70 kinase sequences triggers ca lcium mobilization. Aggregation of the Syk chimera alone, or coaggrega tion of chimeras bearing Fyn and ZAP-70 kinases, suffices to initiate cytolytic effector function. The pattern of tyrosine phosphorylation i nduced by clustering of the Syk chimera is similar to the pattern indu ced by aggregation of T cell receptor.