Protein kinase C delta (PKCδ) is a key molecule in insulin signaling essential for insulin-induced glucose transport in skeletal muscle. Recent studies in our laboratory have shown that insulin rapidly stimulates PKCδ activity and increases PKCδ protein and RNA levels, and that the SP-1 transcription factor is involved in insulin-induced transcription of the PKCδ gene. Activation of SP-1 involves serine phosphorylation and translocation to the nucleus. In this study we examined the possibility that PKCα might be involved in serine phosphorylation and activation of SP-1. We found that insulin rapidly phosphorylates and translocates SP-1. In the cytoplasm, SP-1 was constitutively associated with PKCα, and insulin stimulation caused these proteins to dissociate. In contrast, in the nucleus insulin induced an increase in association between PKCα and SP-1. PKCα inhibition blocked insulin-induced serine phosphorylation of SP-1 and its association with PKCα in the nucleus. Inhibition of PKCα also reduced the insulin-induced increase in PKCδ RNA and protein in the cytoplasmic and nuclear fractions. We also attempted to determine if another transcription factor might be involved in regulation of PKCδ expression. We earlier showed that insulin did not affect nuclear NFκB levels. Inhibition of NFκB, however, increased insulin-induced increase in PKCδ RNA and protein in the cytoplasmic and nuclear fractions. Surprisingly, this inhibition reduced the insulin-induced increase in cytoplasmic and nuclear PKCα RNA and protein. Inhibition of PKCδ reduced IκBα phosphorylation as well as NFκB activation. Thus, PKCα regulates insulin-induced PKCδ expression levels and this regulation involves activation of SP-1 and NFκB.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 5 Jan 2007|
Bibliographical noteFunding Information:
This work was supported in part by the Sorrell Foundation, and grants from D Cure Israel, and the Chief Scientist’s Office of the Israel Ministry of Health. This study represents an essential portion of the thesis submitted by MH-F to Bar-Ilan University in partial fulfillment of the requirements for the Ph.D. degree.
- Gene transcription
- Insulin signaling
- Transcription factors