A Role of the IGF-1 Receptor In Aging

IGF-1 受体在衰老中的作用

• 批准号: 6641119
• 负责人: RENATO Luigi BASERGA
• 金额: $ 29.47万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6641119
• 关键词: binding proteins; biological signal transduction; cell differentiation; cell growth regulation; cell senescence; growth factor receptors; guanine nucleotide binding protein; insulinlike growth factor; longevity; oncoproteins; tissue /cell culture; transcription factor

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.

性状（由申请人提供）：1型胰岛素样生长因子 胰岛素样生长因子受体（IGF-1 R）在衰老中起重要作用。我的实验室 一段时间以来，他一直对IGF-1 R的生物学及其 发信号。最近，我们发现IGF-1 R，直接或间接， 调节三种蛋白质的表达和/或活性， 在体内或体外都与衰老有关。这三 蛋白质是：1）Id蛋白，其是参与以下的转录因子： 控制细胞增殖和细胞分化。Idl蛋白 已经被证明可以延缓细胞衰老。2)Ras癌蛋白， 在某些情况下，在培养的细胞中诱导衰老样状态。 3)Shc蛋白的p66同种型，它在人的寿命中起作用。 小鼠IGF-1 R参与Id基因表达的调控 和Ras的稳定化是我们实验室的原创发现， 完全新颖。p66在IGF-IR信号传导中的作用已经在 其他实验室以及我们的实验室，但很少有信息出现， 远了一个受体和三个信号蛋白的结合， 在老化构成一个领域的调查，结合基本细胞生物学 与衰老的关系该项目需要与at密切互动 本申请中的至少两个其他项目。