Signalling mechanisms of the ShcD adaptor protein

ShcD 接头蛋白的信号传导机制

• 批准号: 327372-2011
• 负责人: Jones, Nina
• 金额: $ 3.5万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572003
• 关键词: Signalling; mechanisms; ShcD; adaptor; protein

Signal transduction is a central process in multicellular organisms that allows for the exchange of informational cues between and within cells. These cues are interpreted by organized networks of protein interactions inside the cell which regulate complex biochemical events, ultimately converting them into biological responses such as growth, migration, differentiation and survival. Cells have evolved a tremendous ability to selectively activate specific downstream pathways, through formation of distinct protein complexes. Understanding the molecular basis of these interactions is therefore a significant challenge in biology. The Shc family of intracellular adaptor proteins provides a unique opportunity to investigate the questions of selectivity and specificity. These proteins function to relay phosphotyrosine-based signals from cell surface receptors to various effector proteins, and they play critical roles in cardiovascular and neural development. Intriguingly, the Shc family has increased in complexity from one gene in flies to several in mammals, and we have recently characterized a fourth mammalian homolog, ShcD. We have found that this adaptor is unique among Shc proteins in its expression pattern and its ability to associate with binding targets, supporting the notion that elaborate diversification of Shc functions has occurred during evolution. Using a combination of biochemical, cellular and genetic approaches, we propose to identify the molecular components and biological functions associated with ShcD. The goal of this study is to dissect the Shc protein signaling paradigm to reveal the mechanisms by which specificity in signal transduction has evolved from a single family of simple adaptor proteins. Our findings may also provide mechanistic insight to explain how perturbations in cellular communication can lead to altered cell function.

信号转导是多细胞生物中的一个中心过程，允许细胞之间和细胞内的信息线索交换。 这些线索由细胞内有组织的蛋白质相互作用网络解释，这些网络调节复杂的生化事件，最终将其转化为生物反应，如生长，迁移，分化和存活。细胞已经进化出了巨大的能力，通过形成不同的蛋白质复合物来选择性地激活特定的下游通路。因此，了解这些相互作用的分子基础是生物学中的一个重大挑战。 Shc家族的细胞内衔接蛋白提供了一个独特的机会，调查的选择性和特异性的问题。 这些蛋白质的功能是将基于磷酸酪氨酸的信号从细胞表面受体传递到各种效应蛋白，并且它们在心血管和神经发育中起关键作用。 有趣的是，Shc家族的复杂性从果蝇中的一个基因增加到哺乳动物中的几个基因，我们最近发现了第四个哺乳动物同源物ShcD。 我们已经发现，这种适配器是独特的Shc蛋白在其表达模式和它的能力与结合目标，支持的概念，精心多样化的Shc功能发生在进化过程中。使用生物化学，细胞和遗传学方法的组合，我们建议确定与ShcD相关的分子组成和生物学功能。 本研究的目的是剖析Shc蛋白信号转导模式，揭示信号转导特异性从一个简单的衔接蛋白家族进化而来的机制。 我们的研究结果也可能提供机制的见解，以解释细胞通讯的扰动如何导致细胞功能的改变。