胰岛素受体底物-5和-6是胰岛素受体的不良底物。

Insulin receptor substrates-5 and -6 are poor substrates for the insulin receptor.

作者信息

Versteyhe Soetkin, Blanquart Christophe, Hampe Cornelia, Mahmood Shaukat, Christeff Nevena, De Meyts Pierre, Gray Steven G, Issad Tarik

机构信息

Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 1070 Brussels, Belgium.

出版信息

Mol Med Rep. 2010 Jan-Feb;3(1):189-93. doi: 10.3892/mmr_00000239.

DOI:10.3892/mmr_00000239

PMID:21472221

Abstract

Insulin receptor substrates (IRS)-5 and -6 are two recently identified members of the IRS family. We investigated their roles as insulin receptor substrates and compared them with Src-homology-2-containing (Shc) protein, a well-established substrate. Bioluminescence resonance energy transfer (BRET) experiments showed no interaction between the receptor and IRS-5, while interaction with IRS-6 was not enhanced by insulin. By contrast, Shc showed an insulin-induced BRET response, as did a truncated form of IRS-1 (1-262). While Shc was heavily phosphorylated after stimulation of the insulin receptor, IRS-5 and -6 showed very weak phosphorylation levels. These results suggest that, although these two adaptors have previously been proposed as substrates for the insulin receptor, they are poor substrates for the insulin receptor. This calls into question their relevance to insulin signalling.

摘要

胰岛素受体底物（IRS）-5和-6是胰岛素受体底物家族中最近发现的两个成员。我们研究了它们作为胰岛素受体底物的作用，并将它们与含Src同源2结构域（Shc）的蛋白（一种公认的底物）进行了比较。生物发光共振能量转移（BRET）实验表明，受体与IRS-5之间没有相互作用，而胰岛素并未增强与IRS-6的相互作用。相比之下，Shc显示出胰岛素诱导的BRET反应，截短形式的IRS-1（1-262）也是如此。虽然胰岛素受体受到刺激后Shc被大量磷酸化，但IRS-5和-6的磷酸化水平非常低。这些结果表明，尽管这两种衔接蛋白此前被认为是胰岛素受体的底物，但它们却是胰岛素受体的不良底物。这使人质疑它们与胰岛素信号传导的相关性。