CDK5/P35 PHOSPHORYLATION

CDK5/P35 磷酸化

• 批准号: 8361496
• 负责人: ANGUS C. NAIRN
• 金额: $ 0.13万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361496
• 关键词: Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; CDK5 gene; Calpain; Complex; Cyclin-Dependent Kinase 5; Funding; Grant; In Vitro; Link; Maps; Mass Spectrum Analysis; Mediating; National Center for Research Resources; Neuraxis; Neurons; Phosphorylation; Phosphorylation Site; Phosphotransferases; Preparation; Principal Investigator; Protein Kinase; Research; Research Infrastructure; Resources; Site; Source; Stress; Structure; United States National Institutes of Health; cost; macromolecule; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cyclin-dependent kinase 5 (cdk5) is a protein kinase that regulates neuronal structure in the central nervous system. It is active only when paired with a regulatory partner; one such partner is known as p35. When stressed, neurons are believed to cause calpain-mediated cleavage of p35 to a smaller form known as p25. Increased levels of p25 are associated with Alzheimer's disease and have also have been linked, along with increased cdk5 activity, to amyotrophic lateral sclerosis. We are exploring phosphorylation of the cdk5/p35 complex since the kinase appears to be regulated by its phosphorylation state. Incubation of kinase preparations in vitro with ATP results in the phosphorylation of at least two sites within p35 and seven sites within cdk5, as analyzed by mass spectrometry. The exact site of phosphorylation has been determined in some cases, while others are currently being mapped. We are also conducting experiments to determine whether autophosphorylation or phosphorylation due to another kinase co-purified with the cdk5/p35 complex is being observed.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 细胞周期蛋白依赖性激酶 5 (cdk5) 是一种调节中枢神经系统神经元结构的蛋白激酶。 它仅在与监管合作伙伴配对时才有效；其中一个合作伙伴被称为 p35。 当受到压力时，神经元被认为会导致钙蛋白酶介导的 p35 裂解为更小的形式，称为 p25。 p25 水平升高与阿尔茨海默病相关，并且与 cdk5 活性升高一起还与肌萎缩侧索硬化症相关。 我们正在探索 cdk5/p35 复合物的磷酸化，因为该激酶似乎受其磷酸化状态的调节。 通过质谱分析，激酶制剂与 ATP 体外孵育导致 p35 内至少两个位点和 cdk5 内至少两个位点磷酸化。 在某些情况下，磷酸化的确切位点已经确定，而其他情况目前正在绘制地图。 我们还在进行实验以确定是否观察到自磷酸化或由于与 cdk5/p35 复合物共纯化的另一种激酶引起的磷酸化。