Protein kinase C (PKC) epsilon enhances the inhibitory effect of TNF alpha on insulin signaling in HEK293 cells.
Recently we have shown that PKC beta1 and beta2 are able to inhibit the tyrosine kinase activity of the human insulin receptor (HIR). Now we have investigated whether a distinct PKC isoform might be involved in the inhibitory effect of TNF alpha on insulin signaling in HEK293 cells. TNF alpha induces a rapid translocation of the PKC isoform epsilon (TNF alpha 10(-9) M, maximal effect within 5-10 min) in rat-1 fibroblasts, while no effect occurred on other isoforms. Cotransfection of HIR with PKC epsilon did not significantly reduce the insulin stimulated receptor kinase activity; however, when cells were incubated with TNF alpha for 10 min (10(-9) M) a 62 +/- 17% (n = 5) inhibition of the insulin receptor kinase activity was observed which was significantly (P<0.01) higher than that observed in cells which were not transfected with PKC (32 +/- 11.5%, n = 5). The data suggest that translocation of PKC epsilon induced by TNF alpha enables this PKC isoform to interact with insulin signaling and to inhibit the insulin receptor kinase activity.
Kellerer
M
M
Eberhard-Karls-Universität, Med. Klinik u. Poliklinik, Abt. IV, Innere Medizin, Tübingen, Germany.
Mushack
J
J
Mischak
H
H
Häring
H U
HU
D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D051381:Rats; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018076:DNA, Complementary; D007328:Insulin; D007329:Insulin Antagonists; D007527:Isoenzymes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C497257:Prkce protein, rat; D011972:Receptor, Insulin; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon