A Role of the IGF-1 Receptor In Aging

IGF-1 受体在衰老中的作用

• 批准号: 6794996
• 负责人: RENATO Luigi BASERGA
• 金额: $ 30.35万
• 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/6794996
• 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.

描述（由申请人提供）：1 型胰岛素样生长因子 众所周知，IGF-1R 受体在衰老过程中发挥着重要作用。我的实验室 一段时间以来，我一直对 IGF-1R 的生物学及其作用感兴趣。 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 无论是在体内还是在体外，都与衰老有关。这三个 蛋白质是： 1) Id 蛋白质，是参与以下过程的转录因子： 细胞增殖和细胞分化的控制。 Idl蛋白 已被证明可以延缓细胞衰老。 2) Ras 癌蛋白， 在某些情况下，会诱导培养细胞出现类衰老状态。 3) Shc 蛋白的 p66 亚型，在长寿中发挥作用 老鼠。 IGF-1R 参与 Id 基因表达的调节 Ras 的稳定性是我们实验室的原创发现 完全新颖。 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，因此 远的。一个受体和三个信号蛋白的组合都参与其中 衰老构成了一个研究领域，结合了基础细胞生物学 以及与衰老的相关性。该项目需要与以下人员密切互动 本申请中至少有两个其他项目。