期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 281, 期 39, 页码 29174-29180出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M603274200
关键词
-
Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway. The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking. We have used liquid chromatography tandem mass spectrometry to identify several 14-3-3 isoforms as AS160-interacting proteins. 14-3-3 proteins interact with AS160 in an insulin- and Akt-dependent manner via an Akt phosphorylation site, Thr-642. This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin- stimulated GLUT4 translocation. Introduction of a constitutive 14-3-3 binding site into AS160(4P) restored 14-3-3 binding without disrupting AS160- IRAP (insulin- responsive amino peptidase) interaction and reversed the inhibitory effect of AS160(4P) on GLUT4 translocation. These data show that the insulin- dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据