Modulation of T cell activation by differential regulation of the phosphorylation of two cytosolic proteins. Implication of both Ca2+ and cyclic AMP-dependent protein kinases.
Interleukin 2 production by activated Jurkat T cells is markedly decreased by prostaglandin E2 (PGE2). The target of PGE2 action has been investigated in the present study. Among the biochemical events occurring after CD3.TCR triggering by anti-CD3 monoclonal antibody, phosphorylation of two cytosolic proteins, pp21 and pp23, was strongly inhibited by PGE2, forskolin, and 8-bromo-cAMP, whereas anti-CD3 monoclonal antibody-induced CD3.TCR modulation and Ca2+ influx were not affected. The inhibition of both pp21 and pp23 phosphorylation and interleukin 2 synthesis by PGE2 can be largely reversed by the cAMP-dependent protein kinase inhibitor, N-[2-(methylamino)-ethyl-1]-5-isoquinoline sulfonamide. Together with the demonstration of a cAMP-dependent protein kinase activity in Jurkat T cells, these results are consistent with the participation of the cAMP-dependent protein kinase mediating the inhibitory action of PGE2, probably through the inhibition of pp21 and pp23 phosphorylation. Thus, it appears that the modulation of the phosphorylation of these cytosolic proteins represents an essential step in the regulation of T lymphocyte activation.
Mary
D
D
Inserm U210, Faculté de Médecine (Pasteur), Nice, France.
Peyron
J F
JF
Auberger
P
P
Aussel
C
C
Fehlmann
M
M
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D005576:Colforsin; D000242:Cyclic AMP; D011494:Protein Kinases; D015232:Dinoprostone; D002118:Calcium