Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain.
A conserved sequence motif has been identified in a number of signaling subunits associated with hematopoietic cell antigen receptors. Here, we characterize signaling by a 17 amino acid motif that is triplicated in the T cell antigen receptor zeta chain. Analysis of zeta truncations and constructs containing the isolated motif demonstrates that this motif is sufficient for the induction of both proximal and distal events associated with T cell activation. Stimulation of truncations that contain either one, two, or three copies of the motif results in induction of an identical pattern of tyrosine phosphoproteins. Moreover, triplication of the NH2-terminal zeta motif results in enhanced signaling, suggesting a redundant role in signal amplification for the three motifs in zeta. Finally, we demonstrate the association of a recently identified protein tyrosine kinase ZAP-70 with this motif, and provide evidence for its involvement in zeta function.
Irving
B A
BA
Department of Physiology, University of California, San Francisco 94143.
Chan
A C
AC
Weiss
A
A
D000595:Amino Acid Sequence; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D005434:Flow Cytometry; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection; D051746:ZAP-70 Protein-Tyrosine Kinase
D016827:CD8 Antigens; D008565:Membrane Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human