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-tyrosine kinase activity. Receptor-associated kinases related to the src proto-oncogene product have been found to be essential for cellular activation and may interact with the cytoplasmic domains of the antigen receptor chains. We show here that anti-CD16 antibody-mediated clustering of chimeric transmembrane proteins bearing a CD16 extracellular domain 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 calcium mobilization. Aggregation of the Syk chimera alone, or coaggregation of chimeras bearing Fyn and ZAP-70 kinases, suffices to initiate cytolytic effector function. The pattern of tyrosine phosphorylation induced by clustering of the Syk chimera is similar to the pattern induced by aggregation of T cell receptor.