Mutagenesis of T cell antigen receptor zeta chain tyrosine residues. Effects on tyrosine phosphorylation and lymphokine production.
Occupancy of the T cell antigen receptor triggers a complex set of events that culminate in cellular activation. It is clear that tyrosine kinases play important roles in this process. The zeta subunit of the T cell antigen receptor is a 16-kDa transmembrane structure that exists primarily as a disulfide-linked homodimer. On receptor activation, a subset of zeta molecules undergo tyrosine phosphorylation. To evaluate this process and the role of zeta phosphorylation in T cell activation, site-specific mutagenesis of the intracytoplasmic tyrosines of zeta has been carried out. Analysis of cells expressing these mutant zeta subunits demonstrated that multiple tyrosines underwent phosphorylation in response to receptor engagement, and that the four most carboxyl tyrosines were most crucial to this process. Despite abnormalities in phosphorylation induced by the mutations, lymphokine production in these transfectants was unaffected. Hence, although zeta is a prominent substrate for a receptor-activated tyrosine kinase, neither the mutation of individual tyrosines nor the alteration of the phosphorylation state of the molecule substantively affected the coupling of T cell receptor activation to lymphokine production. These findings raise questions regarding the role of zeta phosphorylation in T cell activation.
Frank
S J
SJ
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Cenciarelli
C
C
Niklinska
B B
BB
Letourneur
F
F
Ashwell
J D
JD
Weissman
A M
AM
D000818:Animals; D004247:DNA; D006825:Hybridomas; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011233:Precipitin Tests; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism*
D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014443:Tyrosine; D004247:DNA