NCK-ASSOCIATES WITH THE SH2 DOMAIN-DOCKING PROTEIN IRS-1 IN INSULIN-STIMULATED CELLS
NCK-ASSOCIATES WITH THE SH2 DOMAIN-DOCKING PROTEIN IRS-1 IN INSULIN-STIMULATED CELLS
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DOI：
10.1073/pnas.90.24.11713
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发表时间：
1993-12-15
影响因子：
11.1
通讯作者：
SKOLNIK, EY
中科院分区：
文献类型：
--
作者：
LEE, CH;LI, W;SKOLNIK, EY
Nck是由一个SH 2和三个SH 3结构域组成的致癌蛋白，是各种细胞表面受体的共同靶点。Nck被认为是一种衔接蛋白，将细胞表面受体与下游效应分子偶联，调节受体激活诱导的细胞反应。在这份报告中，我们表明，NCK形成一个稳定的复合物在体内与IRS-1在胰岛素刺激的细胞。IRS-1和Nck之间的相互作用是通过Nck的SH 2结构域与酪氨酸磷酸化IRS-1的结合介导的。虽然Nck与IRS-1相关，但Nck磷酸化不受胰岛素刺激的影响。此外，体外和体内研究表明，Nck，GRB 2和p85的SH 2结构域结合IRS-1中不同的磷酸酪氨酸残基。在胰岛素刺激后，可以发现所有三种信号分子与单个IRS-1分子复合。这些发现提供了进一步的证据，即响应于胰岛素刺激，IRS-1作为SH 2对接蛋白，协调由胰岛素受体激活的各种不同信号通路的调节。
Nck, an oncogenic protein composed of one SH2 and three SH3 domains, is a common target for various cell surface receptors. Nck is thought to function as an adaptor protein to couple cell surface receptors to downstream effector molecules that regulate cellular responses induced by receptor activation. In this report, we show that Nck forms a stable complex in vivo with IRS-1 in insulin-stimulated cells. The interaction between IRS-1 and Nck is mediated by the binding of the SH2 domain of Nck to tyrosine-phosphorylated IRS-1. Although Nck associates with IRS-1, Nck phosphorylation is not affected by insulin stimulation. Furthermore, in vitro and in vivo studies show that the SH2 domains of Nck, GRB2, and p85 bind distinct phosphotyrosine residues in IRS-1. After insulin stimulation all three signaling molecules can be found complexed to a single IRS-1 molecule. These findings provide further evidence that, in response to insulin stimulation, IRS-1 acts as an SH2 docking protein that coordinates the regulation of various different signaling pathways activated by the insulin receptor.