Interleukin 2-dependent phosphorylation of interleukin 2 receptors and other T cell membrane proteins.
The addition of IL 2 to Con A-activated splenic T cells induced the rapid and time-dependent phosphorylation of membrane proteins with m.w. of 115,000 to 105,000, 90,000, and 66,000, and to a lesser extent 55,000 to 58,000, 40,000, and 34,000. Immunoprecipitations conducted with an anti-IL 2 receptor antibody indicated that the murine IL 2 receptor (55,000 to 58,000) was included in the set of IL 2-dependent phosphoproteins. Phosphorylation of these same proteins was also seen after IL 2 treatment of PHA-activated T cells and of the IL 2-dependent line CTLL-2. Membrane phosphorylation was dependent on physiologically relevant IL 2 concentrations (0.2 to 1 ng/ml), and was detected as early as 1 min after IL 2 addition, with maximal levels of phosphorylation achieved by 15 min. In contrast to these observations, the pattern of cytoplasmic protein phosphorylation remained unchanged after IL 2 addition, although IL 2 did augment the level of preexisting cytoplasmic phosphorylation induced by lectin. The pattern of membrane protein phosphorylation induced by IL 2 also overlapped in part with that induced after stimulation of Con A-activated T cells with the phorbol ester PMA. IL 2-stimulated phosphorylation was inhibited by the addition of agents that both stimulate cyclic AMP-dependent protein kinases and block lymphocyte mitogenesis. No effect was seen upon addition of agents that enhance cyclic GMP-dependent protein kinases. These observations support a role for specific membrane as opposed to cytoplasmic protein phosphorylation in the regulation of lymphocyte growth by IL 2, and also suggest that protein kinase A, and perhaps protein kinase C, participate as regulators of the IL 2 signaling mechanism.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2 / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000378:metabolism*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D000242:Cyclic AMP; D006152:Cyclic GMP