The zeta isoform of protein kinase C controls interleukin-2-mediated proliferation in a murine T cell line: evidence for an additional role of protein kinase C epsilon and beta.
In order to address a role of protein kinase C in signal transduction through interleukin-2, interleukin-4, and interleukin-9 receptors, we took advantage of the availability of a selective protein kinase C inhibitor, GF109203X, and the availability of TS1 beta and TS1 alpha beta cell lines which can be maintained in interleukin-2, interleukin-4, or interleukin-9 independently. In this report we report that inhibition of protein kinase C activity by GF109203X does not block interleukin-4- or interleukin-9-dependent proliferation and, on the contrary, does block interleukin-2-dependent proliferation, suggesting that interleukin-4 and interleukin-9 do not use signal transduction pathways mediated by protein kinase C and that the common gamma chain of interleukin-2, interleukin-4, and interleukin-9 receptors is not responsible per se for the activation of protein kinase C through interleukin-2 receptor. Moreover, GF109203X induces apoptosis in cells cultured in interleukin-2 but not in interleukin-4 or interleukin-9. Using antisense oligonucleotides, we report that the zeta and epsilon protein kinase C isoforms are involved in signaling through high-affinity interleukin-2 receptor and beta and zeta are involved in signaling through intermediate-affinity interleukin-2 receptor. Taken together, our data indicate that activation of the zeta, beta, and epsilon protein kinase C isoforms is an important step in interleukin-2-mediated proliferation.
Gómez
J
J
Centro de Investigaciones Biológicas, Madrid, Spain.
Pitton
C
C
García
A
A
Martinez de Aragón
A
A
Silva
A
A
Rebollo
A
A
D000818:Animals; D001483:Base Sequence; D002999:Clone Cells; D004247:DNA / Q000032:analysis; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology
D007376:Interleukin-2; D016906:Interleukin-9; D007527:Isoenzymes; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D015847:Interleukin-4; D004247:DNA; D011493:Protein Kinase C