Protein kinase C (PKC) ϵ enhances the inhibitory effect of TNFα on insulin signaling in HEK293 cells

FEBS Letters

Häring, Hans Ulrich²  Mischak, Harald¹  Kellerer, Monika²  Mushack, Joanne² 

[1] Hämatologisches Institut, Marchioninistr. 15, D-81377 Munich, Germany;Eberhard-Karls-Universität, Med. Klinik u. Poliklinik, Abt. IV, Innere Medizin, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany

关键词: Tumor necrosis factor α;    Insulin resistance;    Protein kinase C;    Insulin receptor;    Insulin receptor substrate-1;    PKC;    protein kinase C;    HIR;    human insulin receptor;    IRS-1;    insulin receptor substrate 1;    TNFα;    tumor necrosis factor α;    CHO;    Chinese hamster ovary;    HEK;    human embryonic kidney;    DTT;    dithiothreitol;    FCS;    fetal calf serum;    ECL;    enhanced chemiluminescence;   

DOI  :  10.1016/S0014-5793(97)01357-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recently we have shown that PKC β1 and β2 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 TNFα on insulin signaling in HEK293 cells. TNFα induces a rapid translocation of the PKC isoform ϵ (TNFα 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 ϵ did not significantly reduce the insulin stimulated receptor kinase activity; however, when cells were incubated with TNFα 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 ϵ induced by TNFα enables this PKC isoform to interact with insulin signaling and to inhibit the insulin receptor kinase activity.

【 授权许可】

Unknown