Insulin stimulation of PKCδ triggers its rapid degradation via the ubiquitin-proteasome pathway

Chagit Brand, Miriam Horovitz-Fried, Aya Inbar, Tamar-Brutman-Barazani, Chaya Brodie, Sanford R. Sampson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Insulin rapidly upregulates protein levels of PKCδ in classical insulin target tissues skeletal muscle and liver. Insulin induces both a rapid increase in de novo synthesis of PKCδ protein. In this study we examined the possibility that insulin may also inhibit degradation of PKCδ. Experiments were performed on L6 skeletal muscle myoblasts or myotubes in culture. Phorbol ester (PMA)- and insulin-induced degradation of PKCδ were abrogated by proteasome inhibition. Both PMA and insulin induced ubiquitination of PKCδ, but not of that PKCα or PKCε and increased proteasome activity within 5min. We examined the role of tyrosine phosphorylation of PKCδ in targeting PKCδ for degradation by the ubiquitin-proteasome pathway. Transfection of cells with PKCδY311F, which is not phosphorylated, resulted in abolition of insulin-induced ubiquitination of PKCδ and increase in proteasome activity. We conclude that insulin induces degradation of PKCδ via the ubiquitin-proteasome system, and that this effect requires phosphorylation on specific tyrosine residues for targeting PKCδ for degradation by the ubiquitin-proteasome pathway. These studies provide additional evidence for unique effects of insulin on regulation of PKCδ protein levels.

Original languageEnglish
Pages (from-to)1265-1275
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1803
Issue number11
DOIs
StatePublished - Nov 2010

Bibliographical note

Funding Information:
This work was supported in part by the Russell Berrie Foundation and D-Cure, Diabetes Care in Israel, and grants from the Chief Scientist's Office of the Israel Ministry of Health; and the Sorrell Foundation.

Keywords

  • PKC
  • Proteasome
  • Protein degradation
  • Ubiquitin

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