This Article Full Text Full Text (PDF) All Versions of this Article: 18/5/1287    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weyrich, P. Articles by Lammers, R. Search for Related Content PubMed PubMed Citation Articles by Weyrich, P. Articles by Lammers, R.

Partitioning-Defective Protein 6 Regulates Insulin-Dependent Glycogen Synthesis via Atypical Protein Kinase C

Medical Clinic IV, University of Tübingen, Tübingen 72076, Germany

Address all correspondence and requests for reprints to: Reiner Lammers, Medical Clinic IV, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany. E-mail: reiner.lammers{at}med uni-tuebingen.de.

The atypical isoforms of protein kinase C (aPKCs) play an important role in insulin signaling and are involved in insulin-stimulated glucose uptake in different cell systems. On the other hand, aPKCs also are able to negatively regulate important proteins for insulin signaling, like phosphatidylinositol 3-kinase and protein kinase B/Akt. To find aPKC-interacting proteins that may promote positive or negative activities of aPKCs, a yeast two-hybrid screen was performed. Partitioning-defective protein 6 (Par6) was detected in human cDNA libraries of different adult insulin-sensitive tissues. Although Par6 is known as an aPKC-interacting protein during development, no role for Par6 in insulin signaling has been reported so far. We therefore studied the effects of Par6 overexpression in C2C12 murine myoblasts. In these cells, Par6 associated constitutively with endogenous aPKCs, and the expression level as well as the activity of aPKCs were increased. Insulin-dependent association of the p85 subunit of phosphatidylinositol 3-kinase with insulin receptor substrate 1 was hampered and the phosphorylation of Akt/glycogen synthase kinase-3/ß was significantly impaired after stimulation with insulin or with platelet-derived growth factor. Consequently, insulin-dependent glycogen synthesis was down-regulated (1.44 vs. 2.24 fold, P < 0.01). We therefore suggest that Par6 acts as a negative regulator of the insulin signal.

This article has been cited by other articles:

				P. Labhart, S. Karmakar, E. M. Salicru, B. S. Egan, V. Alexiadis, B. W. O'Malley, and C. L. Smith Identification of target genes in breast cancer cells directly regulated by the SRC-3/AIB1 coactivator PNAS, February 1, 2005; 102(5): 1339 - 1344. [Abstract] [Full Text] [PDF]