%0 Journal Article
%@ 1932-7420
%A Ho, Ping-Chih
%A Lin, Yi-Wei
%A Tsui, Yao-Chen
%A Gupta, Pawan
%A Wei, Li-Na
%D 2009
%F open:1087
%I Cell Press
%J Cell metabolism
%K GLUT4; cytoplasmic RIP140; adipocytes; AS160; Akt; post-translational modification
%N 6
%P 516-23
%T A negative regulatory pathway of GLUT4 trafficking in adipocyte: new function of RIP140 in the cytoplasm via AS160.
%U http://crdd.osdd.net/open/1087/
%V 10
%X Receptor-interacting protein 140 (RIP140), a nuclear receptor corepressor, is important for lipid and glucose metabolism. In adipocytes, RIP140 can be phosphorylated by protein kinase C epsilon (PKCvarepsilon), followed by arginine methylation, and exported to the cytoplasm. This study demonstrates for the first time a cytoplasmic function for RIP140: to counteract insulin-stimulated glucose transporter 4 (GLUT4) membrane partitioning and glucose uptake in adipocytes. Cytoplasmic RIP140 interacts with the Akt substrate AS160, thereby impeding AS160 phosphorylation by Akt; this in turn reduces GLUT4 trafficking. This signal transduction pathway can be recapitulated in the epididymal adipocytes of diet-induced obese mice: nuclear PKCvarepsilon is activated, cytoplasmic RIP140 increases, and GLUT4 trafficking and glucose uptake are reduced. The data reveal a new, cytoplasmic function for RIP140 as a negative regulator of GLUT4 trafficking and glucose uptake, and shed insight into the regulation of basal and insulin-stimulated glucose disposal by a nuclear-initiated counteracting mechanism.
%Z Copyright of this article belongs to Cell Press