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

AbstractRecently 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