The Association of ClipR-59 Protein with AS160 Modulates AS160 Protein Phosphorylation and Adipocyte Glut4 Protein Membrane Translocation
The Association of ClipR-59 Protein with AS160 Modulates AS160 Protein Phosphorylation and Adipocyte Glut4 Protein Membrane Translocation
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DOI：
10.1074/jbc.m112.357699
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发表时间：
2012-08-03
影响因子：
4.8
通讯作者：
Du, Keyong
中科院分区：
文献类型：
--
作者：
Ren, Wenying;Cheema, Sarwat;Du, Keyong
ClipR-59是一种膜相关蛋白，与膜信号传导和囊泡运输有关。最近，我们已经确定ClipR-59作为Akt相互作用蛋白，并且我们发现，通过与Akt相互作用，ClipR-59调节Akt亚细胞区室化和Akt底物AS 160磷酸化，从而促进Glut 4膜转位。在这里，我们进一步研究了ClipR-59对AS 160磷酸化和随后的脂肪细胞葡萄糖转运的调节作用。我们的数据表明ClipR-59与AS 160相互作用，这是由ClipR-59的锚蛋白重复序列介导的，并受胰岛素信号转导的调节。此外，数据还表明ClipR-59与AS 160的相互作用是ClipR-59调节Glut 4膜转位所必需的，因为Delta ANK-ClipR-59（AS 160相互作用缺陷突变体）未能促进3 T3-L1脂肪细胞中胰岛素诱导的AS 160磷酸化、Glut 4膜转位和葡萄糖转运。由于ClipR-59也与Akt相互作用并增强Akt和AS 160之间的相互作用，我们认为ClipR-59作为支架蛋白促进Akt介导的AS 160磷酸化，从而调节葡萄糖转运。
ClipR-59 is a membrane-associated protein and has been implicated in membrane signaling and vesicle trafficking. Recently, we have identified ClipR-59 as an Akt-interacting protein, and we have found that, by interacting with Akt, ClipR-59 modulates Akt subcellular compartmentalization and Akt substrate AS160 phosphorylation, thereby promoting Glut4 membrane translocation. Here, we have further investigated the regulatory effects of ClipR-59 on AS160 phosphorylation and subsequent adipocyte glucose transport. Our data showed that ClipR-59 interacted with AS160, which was mediated by the ankyrin repeats of ClipR-59 and regulated by insulin signaling. Moreover, the data also demonstrated that the interaction of ClipR-59 with AS160 was required for ClipR-59 to modulate Glut4 membrane translocation as Delta ANK-ClipR-59, an AS160 interaction-defective mutant, failed to promote AS160 phosphorylation, Glut4 membrane translocation, and glucose transport induced by insulin in 3T3-L1 adipocytes. Because ClipR-59 also interacts with Akt and enhances the interaction between Akt and AS160, we suggest that ClipR-59 functions as a scaffold protein to facilitate Akt-mediated AS160 phosphorylation, thereby regulating glucose transport.