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 protooncogene 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.
Kolanus
W
W
Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Romeo
C
C
Seed
B
B
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002678:Chimera; D006801:Humans; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D011940:Receptor Aggregation / Q000276:immunology*; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*
D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D002118:Calcium