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Protein kinase C (PKC) ϵ enhances the inhibitory effect of TNFα on insulin signaling in HEK293 cells
Author(s) -
Kellerer Monika,
Mushack Joanne,
Mischak Harald,
Häring Hans Ulrich
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01357-4
Subject(s) - hek 293 cells , protein kinase c , microbiology and biotechnology , chemistry , inhibitory postsynaptic potential , signal transduction , biology , biochemistry , endocrinology , gene
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.