Hormonal mechanisms of gene regulation

胰岛素除了控制我们身体对糖的使用外，还控制着各种组织中细胞的新陈代谢和生长。它通过调节特定基因的表达来实现这一功能。由于这些基因存在于细胞核中，而胰岛素通过与细胞表面的受体结合而起作用，因此必须激活一系列将信号从细胞表面传递到细胞核的事件。本研究的目的是研究形成这一信号级联部分的特定中介蛋白。首先，我们将确定这种级联反应的新途径的成员，这是激活MAP激酶（一种易位到细胞核并刺激基因表达的蛋白质）所必需的。其次，我们将检查adp核糖基化。这个过程是由一种尚未被描述的酶控制的。此外，它调节了许多不同的途径，每个途径都与一组不同的基因相关。了解这两个过程将极大地增强我们干预该系统的能力，并最终使我们能够选择性地针对胰岛素刺激的负面特征，而不干扰其积极功能。

Insulin, in addition to controlling our body's use of sugars, controls the metabolism and growth of cells in various tissues. It accomplishes this function by modulating the expression of specific genes. Since the genes are present in the nucleus, and insulin operates by binding to receptors on the cell surface, a cascade of events that transduce the signal from the cell surface in to the nucleus must be activated. This study has been designed to examine specific mediator proteins that form part of this signalling cascade. First, we will be identifying members of a novel pathway of this cascade that is required for activation of MAP kinase, a protein that translocates into the cell nucleus and stimulates gene expression. Second, we will examine ADP-ribosylation. This process is controlled by an enzyme that has not been characterized. Furthermore, it regulates a number of distinct pathways, each associated with a different set of genes. Understanding these two processes will greatly enhance our ability to intervene in this system and eventually allow us to selectively target the negative features of insulin stimulation without interfering with its positive functions.