Protein kinase C regulates both production and secretion of interleukin 2.
Inhibiting protein kinase C (PKC) activity abrogated interleukin 2 (IL2) production by mitogen-stimulated human T lymphocytes. This effect was due partially to a 50% decrease in IL2 gene expression. However, when PKC inhibitors were added after IL2 gene transcription had already proceeded for 3-4 h, the IL2 in the culture supernatants was still reduced by 30-80%, and intracellular IL2 was increased by up to 50%. The inhibition of PKC affected the expression of IL2 receptors by these cells differently; it had little effect on gene expression or on the membrane-bound form of the receptor, but it decreased soluble receptors in the supernatants by 50-80%. These data indicate that in addition to its previously defined role in gene expression, PKC can also regulate extracellular secretion of proteins critical for T cell proliferation.
Modiano
J F
JF
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Kolp
R
R
Lamb
R J
RJ
Nowell
P C
PC
D000470:Alkaloids / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000235:genetics; D019311:Staurosporine; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism
D000470:Alkaloids; D007376:Interleukin-2; D008934:Mitogens; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D012313:RNA; D011493:Protein Kinase C; D019311:Staurosporine