CDK5/P35 PHOSPHORYLATION

CDK5/P35 磷酸化

• 批准号: 7722200
• 负责人: ANGUS C. NAIRN
• 金额: $ 0.11万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722200
• 关键词: Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Calpain; Complex; Computer Retrieval of Information on Scientific Projects Database; Cyclin-Dependent Kinase 5; Funding; Grant; In Vitro; Institution; Link; Maps; Mass Spectrum Analysis; Mediating; Neuraxis; Neurons; Phosphorylation; Phosphorylation Site; Phosphotransferases; Preparation; Protein Kinase; Research; Research Personnel; Resources; Site; Source; Stress; Structure; United States National Institutes of Health; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞周期蛋白依赖性激酶5（cdk 5）是一种调节中枢神经系统神经元结构的蛋白激酶。 它只有在与一个调控伙伴配对时才有活性;这样的伙伴之一被称为p35。 当受到压力时，神经元被认为会引起钙蛋白酶介导的p35分裂成较小的形式，称为p25。 p25水平的增加与阿尔茨海默病有关，并且还与cdk 5活性的增加沿着与肌萎缩侧索硬化症有关。 我们正在探索cdk 5/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。 体外孵育的激酶制剂与ATP的结果在磷酸化的至少两个网站内p35和7个网站内cdk 5，通过质谱分析。 在某些情况下，磷酸化的确切位点已经确定，而其他人目前正在绘制。 我们也正在进行实验，以确定是否观察到由于与cdk 5/p35复合物共纯化的另一种激酶引起的自磷酸化或磷酸化。