Myers M G, White M F
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Annu Rev Pharmacol Toxicol. 1996;36:615-58. doi: 10.1146/annurev.pa.36.040196.003151.
Insulin controls organismal and cellular physiology by initiating numerous intracellular signals. Insulin first binds the extracellular domain of the insulin receptor, which activates the receptor's intracellular tyrosine kinase. Receptor-mediated phosphorylation of the IRS proteins is required for the propagation of signals for mitogenesis, glucose transport, and numerous other biological and biochemical events during insulin signaling. IRS proteins also mediate signaling by a subset of other growth factor and cytokine receptors; recognition and phosphorylation by specific receptors appears to be mediated by the PH and PTB domains of the IRS proteins. The best understood mechanism of IRS-protein-mediated signaling is the binding of SH2 domain-containing signaling molecules (such as PI 3'-kinase) by tyrosine phosphorylation sites on IRS proteins. Other paradigms of IRS-protein signaling are beginning to emerge, however, and these exciting molecules promise to teach us much in the next few years.
胰岛素通过启动众多细胞内信号来控制机体和细胞的生理功能。胰岛素首先结合胰岛素受体的细胞外结构域，从而激活受体的细胞内酪氨酸激酶。受体介导的IRS蛋白磷酸化是胰岛素信号传导过程中丝裂原生成、葡萄糖转运以及许多其他生物学和生化事件信号传播所必需的。IRS蛋白还介导其他一些生长因子和细胞因子受体的信号传导；特定受体的识别和磷酸化似乎由IRS蛋白的PH和PTB结构域介导。目前对IRS蛋白介导信号传导机制了解最多的是IRS蛋白上的酪氨酸磷酸化位点与含SH2结构域的信号分子（如PI 3'-激酶）的结合。然而，IRS蛋白信号传导的其他模式也开始出现，这些令人兴奋的分子有望在未来几年为我们提供更多信息。
