title: Protein kinase C (PKC) epsilon enhances the inhibitory effect of TNF alpha on insulin signaling in HEK293 cells.
abstract: 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.
authors.affiliation: Eberhard-Karls-Universität, Med. Klinik u. Poliklinik, Abt. IV, Innere Medizin, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kellerer
authors.forename: J
authors.initials: J
authors.lastname: Mushack
authors.forename: H
authors.initials: H
authors.lastname: Mischak
authors.forename: H U
authors.initials: HU
authors.lastname: Häring
mesh_terms: 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*
chemical_list: 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