Protein kinase Cα regulates insulin receptor signaling in skeletal muscle

Michal Cipok, Shlomit Aga-Mizrachi, Asia Bak, Tamar Feurstein, Rivka Steinhart, Chaya Brodie, Sanford R. Sampson

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Certain PKC isoforms are stimulated by insulin and interact with IR as well as with IRS, but it is still not clear if specific PKC isoforms regulate IR signaling directly or through IRS-1. PKCα may regulate IRS activity in response to insulin. We investigated the possibility that PKCα may be important in insulin signaling. Studies were conducted on skeletal muscle in adult mice and on L6 skeletal cells. PKCα is constitutively associated with IRS-1, and insulin stimulation of PKCα causes disassociation of the two proteins within 5 min. Blockade of PKCα inhibited insulin-induced disassociation of PKCα from IRS1. Selective inhibition of PKCα increased the ability of insulin to reduce blood glucose levels. Insulin stimulation activates PKB and increases the association of PKCα with PKB. Blockade of PKCα increased threonine phosphorylation of PKB. We suggest that PKCα regulates insulin signaling in skeletal muscle through its disassociation from IRS-1 and association with PKB.

Original languageEnglish
Pages (from-to)817-824
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume345
Issue number2
DOIs
StatePublished - 30 Jun 2006

Bibliographical note

Funding Information:
This work was supported in part by Russell Berrie Foundation and D-Cure, Diabetes Care in Israel, the Sorrell Foundation, and the Chief Scientist’s Office of the Israel Ministry of Health. S.R.S. is the incumbent of the Louis Fisher Chair in Cellular Pathology. This study represents an essential portion of the thesis submitted by M.C. in partial fulfillment of the requirements for the Ph. D. degree at Bar-llan University.

Funding

This work was supported in part by Russell Berrie Foundation and D-Cure, Diabetes Care in Israel, the Sorrell Foundation, and the Chief Scientist’s Office of the Israel Ministry of Health. S.R.S. is the incumbent of the Louis Fisher Chair in Cellular Pathology. This study represents an essential portion of the thesis submitted by M.C. in partial fulfillment of the requirements for the Ph. D. degree at Bar-llan University.

FundersFunder number
Diabetes Care in Israel
Sorrell Foundation
Office of the Chief Scientist, Ministry of Health
Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology

    Keywords

    • Blood glucose
    • IRS-1
    • Insulin signaling
    • PKB
    • PKCα
    • Serine phosphorylation
    • Threonine phosphorylation

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