Induction of cAMP-dependent protein kinase (PKA) activity in T cells after stimulation of the prostaglandin E2 or the beta-adrenergic receptors: relationship between PKA activity and inhibition of anti-CD3 monoclonal antibody-induced T cell proliferation.
Recently, we have shown that T cells exposed to concentrations of prostaglandin E2 (PGE2) or the beta-adrenergic receptor agonist isoproterenol (ISO) that elicit equimolar levels of cAMP accumulation do not inhibit anti-CD3 monoclonal antibody-induced T cell proliferation to the same extent. This report extends these studies by investigating the induction of cAMP-dependent protein kinase (PKA) in T cells stimulated with PGE2 or ISO. The kinetics of PKA activity induced by PGE2 or ISO in T cells are similar but PGE2 induces more PKA activity. When T cells were treated with concentrations of PGE2 or ISO that elicited similar PKA activities, PGE2 was found to be more immunosuppressive than ISO. T cells stimulated with PGE2 or ISO showed similar levels of increased PKA activity in both the cytosolic and the particulate fractions. Quantitation of the activity of PKA I and PKA II isozymes in T cells stimulated with PGE2 or ISO revealed that both types were activated; however, while PGE2 induced the utilization of an equal amount of both isozymes in T cells, ISO-treated cells utilized twice as much PKA I compared to PKA II. Overall, these results suggest that qualitative differences in the concentration of cAMP and PKA activity are important elements in modulatory T cell proliferative responses.
Bauman
G P
GP
Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington 40536-0084.
Bartik
M M
MM
Brooks
W H
WH
Roszman
T L
TL
D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002451:Cell Compartmentation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis* / Q000378:metabolism; D015232:Dinoprostone / Q000276:immunology; D004789:Enzyme Activation; D004790:Enzyme Induction; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D007545:Isoproterenol / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D011943:Receptors, Adrenergic, beta / Q000276:immunology*; D018078:Receptors, Prostaglandin E / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007527:Isoenzymes; D011943:Receptors, Adrenergic, beta; D018078:Receptors, Prostaglandin E; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D007545:Isoproterenol