Insulin leads to a parallel translocation of PI-3-kinase and protein kinase C ζ

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Abstract
Protein kinase C consists of a family of at least 12 isoforms which exhibit clear differences in their cofactor dependence and responsiveness to phospholipids. Insulin effects on PKC translocation/activation are now clearly established but responsiveness to this hormone was observed so far only for the classical PKC-isoforms a and β. While activation of the classical PKC's requires Ca2+ and occurs mainly through Diacylglycerol (DAG), stimulation of the atypical isoform PKC-ζ appears to function through a different mechanism involving PI-3-kinase activation. In the present study we used rat-1 fibroblasts stably over-expressing human insulin receptor to investigate whether insulin can activate PKC-ζ and whether such an effect might be related to insulin's effect on PI-3-kinase. After stimulation of the cells with insulin (10−7 mol/1) for one to ten minutes, a rapid translocation of PKC-ζ to the plasma membrane was detectable, as determined by immunoblotting of plasma membrane proteins with antibodies against PKC-ζ. In parallel immunoblots applying antibodies against the regulatory subunit of PI-3-kinase (p85), an insulin-induced translocation of p85 was detectable within one minute after stimulation. The translocation of p85 was associated with an increase in PI-3-kinase activity at the plasma membrane. The data show that insulin stimulates translocation of PKC-ζ in rat-1 fibroblasts. The parallel kinetics of PI-3-kinase translocation/activation and PKC-ζ translocation are compatible with the idea that the insulin effect on PKC-ζ is transduced through PI-3-kinase activation.

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