Regulation of ERK Signalling by the Scaffold Protein KSR1

支架蛋白 KSR1 对 ERK 信号传导的调节

• 批准号: G0600790/1
• 负责人: Jurgen Muller
• 金额: $ 34.03万
• 依托单位: Bangor University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600790%2F1
• 关键词: Regulation; ERK; Signalling; Scaffold; Protein

Mammalian cells contain several signalling pathways that allow them to react to changes in their environment. One of the best-described signalling molecules is the Ras protein, a critical regulator of cellular proliferation, differentiation and survival in multicellular organisms. A major route by which Ras transmits cellular signals is through the sequential activation of the protein kinases Raf-1, MEK and ERK. Activation of this pathway often results in progression through the cell cycle and subsequent cellular proliferation. Because of its central role in growth regulation of mammalian cells, this pathway has to be precisely regulated and defects in its regulation have been attributed to many diseases, including cancer. Scaffold proteins provide spatial and temporal control to cellular signalling by directing associated proteins to specific compartments of the cell. In addition, they physically link several components of a pathway and can exclude others from the complex. In this proposal, we aim to characterise the role of the scaffold protein KSR1 in the regulation of ERK activity after growth factor stimulation of mammalian cells. These studies will provide new insight into the regulation of the ERK signal transduction pathway and will help to understand the processes that cause proliferative diseases like cancer.

哺乳动物细胞含有几种信号通路，使它们能够对环境的变化做出反应。Ras蛋白是描述最多的信号分子之一，它是多细胞生物体中细胞增殖、分化和存活的关键调节因子。Ras传递细胞信号的主要途径是通过蛋白激酶Raf-1、MEK和ERK的顺序激活。该途径的激活通常导致通过细胞周期和随后的细胞增殖的进展。由于其在哺乳动物细胞生长调节中的核心作用，该途径必须被精确调节，并且其调节的缺陷已被归因于许多疾病，包括癌症。支架蛋白通过将相关蛋白引导至细胞的特定区室来提供对细胞信号传导的空间和时间控制。此外，它们在物理上连接通路的几个组分，并可以将其他组分排除在复合物之外。在这个建议中，我们的目标是验证支架蛋白KSR 1在哺乳动物细胞生长因子刺激后ERK活性调节中的作用。这些研究将为ERK信号转导通路的调节提供新的见解，并将有助于了解导致癌症等增殖性疾病的过程。