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Protein kinases that phosphorylate and regulate eIF2B

磷酸化和调节 eIF2B 的蛋白激酶

基本信息

批准号：
BB/D000106/1
负责人：
Graham Pavitt
金额：
$ 39.78万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FD000106%2F1
关键词：
Protein kinases phosphorylate regulate eIF2B

项目摘要

Interactions between proteins modulate essential cell functions ensuring that cells can grow and perform their tasks. Each protein is like a piece in a machine, each must be in the correct place and act at the correct time with all the other parts for the machine to function properly. But unlike most machines and their parts, proteins are continually renewed, move and can be modified to alter their function and/or location. Many proteins act together as parts of protein complexes with a common function. One group of proteins relevant to this proposal is required make (or synthesize) all new proteins in the cell. These are called protein synthesis factors. By increasing or reducing the activity of some of the protein synthesis factors cells can control exactly what new proteins are made at any one time. One common way to alter the activity of proteins is by the addition of phosphate groups to specific places on the surface of the protein. This is called phosphorylation and is performed by a class of proteins called protein kinases. Each kinase responds to specific signals that tell it when to act. We have found that one key protein synthesis factor called eIF2B is phosphorylated at multiple sites, and that this phosphorylation enhances the activity of eIF2B. We are proposing here a series of experiments designed to discover which of the protein kinases present in the cell is responsible for each phosphorylation and to discover how each modification alters eIF2B function in the cell. In yeast cells there are 122 protein kinases. Using modern technologies we will be able to assess the role each one plays in control of eIF2B simultaneously. eIF2B function is also inhibited by phosphorylation of a second protein synthesis factor called eIF2. eIF2 is known to be phosphorylated at a single site called ser51 in response to diverse cell stresses. We have already determined that three of the five parts (or subunits) of eIF2B are all needed to correctly detect whether or not eIF2 is phosphorylated at this key regulatory site. But how exactly do these three subunits of eIF2B act together to do this? In a second series of experiments we propose to use a combination of genetic and biochemistry tools to address this question. This work will provide important detailed molecular information on how the activities of these essential proteins are controlled by phosphorylation.

蛋白质之间的相互作用调节细胞的基本功能，确保细胞能够生长和完成任务。每一种蛋白质就像机器中的一块，每一块都必须在正确的位置，并在正确的时间与所有其他部分一起工作，机器才能正常工作。但与大多数机器及其部件不同的是，蛋白质不断更新、移动，并可以被修改以改变它们的功能和/或位置。许多蛋白质作为具有共同功能的蛋白质复合体的一部分共同作用。与这一提议相关的一组蛋白质需要在细胞中制造(或合成)所有新的蛋白质。这些被称为蛋白质合成因子。通过增加或减少某些蛋白质合成因子的活性，细胞可以在任何时候精确地控制产生什么新的蛋白质。改变蛋白质活性的一种常见方法是在蛋白质表面的特定位置添加磷酸基团。这一过程被称为磷酸化，由一类名为蛋白激酶的蛋白质执行。每个激酶对特定的信号做出反应，这些信号告诉它何时采取行动。我们发现一个关键的蛋白质合成因子eIF2B在多个位点被磷酸化，这种磷酸化增强了eIF2B的活性。我们在这里提出了一系列实验，旨在发现细胞中存在的哪种蛋白激酶负责每一次磷酸化，并发现每一次修饰如何改变细胞中eIF2B的功能。在酵母细胞中，有122种蛋白激酶。使用现代技术，我们将能够同时评估每个人在控制eIF2B方面所发挥的作用。第二种蛋白质合成因子eIF2的磷酸化也抑制了eIF2B的功能。已知eIF2在一个名为ser51的位置被磷酸化，以响应不同的细胞压力。我们已经确定eIF2B的五个部分(或亚基)中的三个都是正确检测eIF2在这个关键调控位点是否被磷酸化所必需的。但eIF2B的这三个亚单位究竟是如何共同作用的呢？在第二系列实验中，我们建议使用遗传和生物化学工具的组合来解决这个问题。这项工作将为这些必需蛋白质的活性如何被磷酸化控制提供重要的详细的分子信息。