Insulin increases nuclear protein kinase Cdelta in L6 skeletal muscle cells.
Protein kinase C (PKC) isoforms are involved in the transduction of a number of signals important for the regulation of cell growth, differentiation, apoptosis, and other cellular functions. PKC proteins reside in the cytoplasm in an inactive state translocate to various membranes to become fully activated in the presence of specific cofactors. Recent evidence indicates that PKC isoforms have an important role in the nucleus. We recently showed that insulin rapidly increases PKCdelta RNA and protein. In this study we initially found that insulin induces an increase in PKCdelta protein in the nuclear fraction. We therefore attempted to elucidate the mechanism of the insulin-induced increase in nuclear PKCdelta. Studies were performed on L6 skeletal myoblasts and myotubes. The increase in nuclear PKCdelta appeared to be unique to insulin because it was not induced by other growth factors or rosiglitazone. Inhibition of transcription or translation blocked the insulin-induced increase in nuclear PKCdelta, whereas inhibition of protein import did not. Inhibition of protein export from the nucleus reduced the insulin-induced increase in PKCdelta in the cytoplasm and increased it in the nucleus. The increase in nuclear PKCdelta induced by insulin was reduced but not abrogated by treatment of isolated nuclei by trypsin digestion. Finally, we showed that insulin induced incorporation of (35)S-methionine into nuclear PKCdelta protein; this effect was not blocked by inhibition of nuclear import. Thus, these results suggest that insulin may induce nuclear-associated, or possibly nuclear, translation of PKCdelta protein.
Horovitz-Fried
Miriam
M
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Brutman-Barazani
Tamar
T
Kesten
Dov
D
Sampson
Sanford R
SR
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology*; D008715:Methionine / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats
D007328:Insulin; D008715:Methionine; C497260:Prkcd protein, rat; D051745:Protein Kinase C-delta