ZAP-70 is constitutively associated with tyrosine-phosphorylated TCR zeta in murine thymocytes and lymph node T cells.
Studies with T cell lines and clones have shown that engagement of the TCR results in the tyrosine phosphorylation of the TCR subunits. This leads to the recruitment of the ZAP-70 protein tyrosine kinase, an interaction involving the two SH2-domains of ZAP-70 with tyrosine-phosphorylated zeta and CD3. However, as previously described, murine thymocytes and lymph node T cells express a constitutively tyrosine-phosphorylated zeta subunit in the basal state. Here, we show that a fraction of ZAP-70 molecules are constitutively associated with tyrosine-phosphorylated zeta. TCR ligation promotes a large increase in the tyrosine phosphorylation of ZAP-70 as well as other TCR subunits. Genetic studies reveal that the constitutive ZAP-70 association with tyrosine-phosphorylated zeta does not absolutely require either TCR or coreceptor interactions with MHC molecules.
van Oers
N S
NS
Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
Killeen
N
N
Weiss
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse