Interaction of insulin receptor substrate-2 (IRS-2) with the insulin and insulin-like growth factor I receptors - Evidence for two distinct phosphotyrosine-dependent interaction domains within IRS-2
Interaction of insulin receptor substrate-2 (IRS-2) with the insulin and insulin-like growth factor I receptors - Evidence for two distinct phosphotyrosine-dependent interaction domains within IRS-2
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DOI：
10.1074/jbc.271.20.11641
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发表时间：
1996-05-17
影响因子：
4.8
通讯作者：
Gustafson, TA
中科院分区：
文献类型：
--
作者：
He, WM;Craparo, A;Gustafson, TA
胰岛素受体底物2（Insulin receptor substrate 2，IRS-2）是胰岛素受体（insulin receptor，IR）的底物。本研究利用酵母双杂交系统和体外相互作用实验，证明IRS-2与IR和胰岛素样生长因子I受体（insulin-like growth factor I receptor，IGF I receptor，IGF I receptor）直接相互作用。IRS-2中含有假定的磷酸酪氨酸结合和SAIN元件（188-591）的区域足以与受体相互作用，并且这种相互作用依赖于NPX（p）Y（其中（p）Y是磷酸酪氨酸）基序。除了该氨基末端NPX（p）Y结合结构域之外，在IRS-2的中心区域中鉴定了另一个强相互作用的结构域，其位于氨基酸591和733之间，发现这种相互作用依赖于受体磷酸化，但不依赖于NPX（p）Y。该区域似乎没有SH 2或磷酸酪氨酸结合结构域。这两种相互作用也可以用IRS-2谷胱甘肽S-转移酶融合蛋白在体外证明。我们得出结论，IRS-2与IRS-1不同，可以通过多个独立的结合基序与酪氨酸磷酸化受体如IR和胰岛素样生长因子I受体相互作用，我们的研究结果表明，在IRS-2的中心区域存在一个以前未鉴定的磷酸酪氨酸依赖性结合结构域。
Insulin receptor substrate 2 (IRS-2) has recently been shown to be a substrate of the insulin receptor (IR), In this study we utilize the yeast two-hybrid system and assays of in vitro interaction to demonstrate that IRS-2 interacts directly with the IR and the insulin-like growth factor I receptor, We show that, like IRS-1, the region of IRS-2 that contains the putative phosphotyrosine binding and SAIN elements (188-591) is sufficient for receptor interaction and that this interaction is dependent upon the NPX(p)Y (where (p)Y is phosphotyrosine) motifs within the juxtamembrane domains of the receptors, In addition to this amino-terminal NPX(p)Y-binding domain, an additional domain of strong interaction was identified in the central region of IRS-2 and was localized between amino acids 591 and 733, This interaction was found to be dependent upon receptor phosphorylation but was NPX(p)Y-independent, This region does not appear to have either an SH2 or a phosphotyrosine binding domain, Both of the interactions could also be demonstrated in vitro using IRS-2 glutathione S-transferase fusion proteins, We conclude that IRS-2, unlike IRS-1, can interact with tyrosine phosphorylated receptors such as the IR and insulin-like growth factor I receptor via multiple independent binding motifs, Our findings suggest the existence of a previously unidentified phosphotyrosine dependent binding domain within the central region of IRS-2.