Implication of protein kinase C in IL-2-mediated proliferation and apoptosis in a murine T cell clone.
Several reports have suggested that protein kinase C plays an essential role in T cell activation and apoptosis. The recent synthesis of the selective protein kinase C inhibitor, GF109203X, has made it possible to test the relevance of protein kinase C in T cell proliferation and apoptosis. We report that the use of GF109203X, in concentrations that are below its toxicity limits, inhibits IL-2-dependent proliferation in murine T cells expressing intermediate or high-affinity IL-2R (TS1 beta and TS1 alpha beta). In addition, GF109203X reverts the suppression of apoptosis mediated by IL-2 or IL-2+ dexamethasone. The use of the phorbol ester PMA, a protein kinase C activator, allows a bypass of the IL-2/IL-2R interaction in the suppression of apoptosis mediated by dexamethasone or IL-2 withdrawal in TS1 beta cells but not in TS1 alpha beta cells. Taken together, our data indicate that activation of protein kinase C is an important step in IL-2-mediated proliferation and in suppression of apoptosis.
Gómez
J
J
Centro de Investigaciones Biológicas, Madrid, Spain.
de la Hera
A
A
Silva
A
A
Pitton
C
C
Garcia
A
A
Rebello
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002999:Clone Cells; D004249:DNA Damage; D005434:Flow Cytometry; D007211:Indoles / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes; D013997:Time Factors
D007211:Indoles; D007376:Interleukin-2; D008301:Maleimides; D015375:Receptors, Interleukin-2; D011493:Protein Kinase C; C070515:bisindolylmaleimide I