CDK5/P35 PHOSPHORYLATION

CDK5/P35 磷酸化

• 批准号: 8169111
• 负责人: ANGUS C. NAIRN
• 金额: $ 0.12万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169111
• 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Cyclin依赖性激酶5（CDK5）是一种调节中枢神经系统中神经元结构的蛋白激酶。 它只有与监管伙伴配对时才活跃。一个这样的伙伴被称为p35。 当受到压力时，据信神经元会导致p35的钙蛋白酶介导的裂解对较小的形式，称为p25。 p25水平的升高与阿尔茨海默氏病有关，并且也与CDK5活性增加与肌萎缩性侧性硬化有关。 我们正在探索CDK5/p35复合物的磷酸化，因为激酶似乎受其磷酸化状态调节。 通过质谱法分析，在体外与ATP的激酶制剂与ATP的体外孵育至少在p35和CDK5内的七个位点的磷酸化。 在某些情况下，已经确定了磷酸化的确切位点，而其他磷酸化位点正在映射。 我们还在进行实验，以确定是否正在观察到与CDK5/p35复合物共纯化的另一个激酶引起的自磷酸化或磷酸化。