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

被引:6
作者
Brand, Chagit [1 ]
Horovitz-Fried, Miriam [1 ]
Inbar, Aya [1 ]
Tamar-Brutman-Barazani [1 ]
Brodie, Chaya [1 ]
Sampson, Sanford R. [1 ]
机构
[1] Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2010年 / 1803卷 / 11期
关键词
PKC; Protein degradation; Proteasome; Ubiquitin; PROTEIN-KINASE-C; DOWN-REGULATION; TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE-1; GLUCOSE-TRANSPORT; INDUCED APOPTOSIS; PRIMARY CULTURES; PLASMA-MEMBRANE; MUSCLE-CELLS; ACTIVATION;
D O I
10.1016/j.bbamcr.2010.07.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Insulin rapidly upregulates protein levels of PKC delta in classical insulin target tissues skeletal muscle and liver. Insulin induces both a rapid increase in de novo synthesis of PKC delta protein. In this study we examined the possibility that insulin may also inhibit degradation of PKC delta. Experiments were performed on L6 skeletal muscle myoblasts or myotubes in culture. Phorbol ester (PMA)- and insulin-induced degradation of PKC delta were abrogated by proteasome inhibition. Both PMA and insulin induced ubiquitination of PKC delta, but not of that PKC alpha or PKC epsilon and increased proteasome activity within 5 min. We examined the role of tyrosine phosphorylation of PKC delta in targeting PKC delta for degradation by the ubiquitin-proteasome pathway. Transfection of cells with PKC delta(YF)-F-311, which is not phosphorylated, resulted in abolition of insulin-induced ubiquitination of PKC delta and increase in proteasome activity. We conclude that insulin induces degradation of PKC delta via the ubiquitin-proteasome system, and that this effect requires phosphorylation on specific tyrosine residues for targeting PKC delta for degradation by the ubiquitin-proteasome pathway. These studies provide additional evidence for unique effects of insulin on regulation of PKC delta protein levels. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:1265 / 1275
页数:11
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