A Role of the IGF-1 Receptor In Aging

说明(申请人提供)：1型胰岛素样生长因子 胰岛素样生长因子受体(IGF-1R)在衰老过程中起重要作用。我的实验室 一段时间以来一直对IGF-1R的生物学及其 发信号。最近，我们发现IGF-1R直接或间接地， 调节三种蛋白质的表达和/或活性，所有这些蛋白质 无论是在体内还是体外，都与衰老有关。这三个人 蛋白质是：1)ID蛋白，它是参与 细胞增殖和分化的调控。IDL蛋白 已被证明可以延缓细胞衰老。2)RAS癌蛋白，它在 在某些情况下，在培养的细胞中会诱导一种类似衰老的状态。 3)Shc蛋白的p66异构体，它在长寿中起作用 老鼠。IGF-1R参与ID基因表达的调控 RAS的稳定是我们实验室独创的发现， 完全新奇。P66在IGF-IR信号转导中的作用已在 其他实验室以及我们的实验室，但出现的信息很少 远远的。一个受体和三个信号蛋白的结合都涉及到 在衰老方面构成了一个研究领域，它结合了基本的细胞生物学 以及与衰老的相关性。此项目需要与At密切互动 本申请中至少还有另外两个项目。

DESCRIPTION (provided by applicant): The type 1 insulin-like growth factor receptor (IGF-1R) is known to play an important role in aging. My laboratory has been interested for some time in the biology of the IGF-1R and its signaling. Recently, we have found that the IGF-1R, directly or indirectly, modulates the expression and/or the activity of three proteins, all of which have been implicated in aging, either in vivo or in vitro. These three proteins are: 1) the Id proteins, that are transcriptional factors involved in the control of cell proliferation and cell differentiation. The Idl protein has been shown to delay cellular senescence. 2) the Ras oncoprotein, which, in certain circumstances, induces a senescent-like state in cells in culture. 3) the p66 isoform of the Shc proteins, that plays a role in the longevity of mice. The involvement of the IGF-1R in the regulation of Id gene expression and the stabilization of Ras are findings original in our laboratory and completely novel. The role of p66 in IGF-IR signaling has been studied in other laboratories as well as ours, but very little information has emerged so far. The combination of a receptor and three signaling proteins all involved in aging constitute an area of investigation, that combines basic cell biology and relevance to aging. This project requires a close interaction with at least two other projects in the present application.