Regulation of Protein Phosphatase Inhibitor-1 by Cdk5

Cdk5 对蛋白磷酸酶抑制剂-1 的调节

• 批准号: 7071780
• 负责人: BAOCHAN NGUYEN
• 金额: $ 3.07万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7071780
• 关键词: biological signal transduction; calcineurin; cyclin dependent kinase; enzyme inhibitors; hippocampus; laboratory mouse; molecular psychobiology; neural plasticity; neuropharmacologic agent; neuropharmacology; neurophysiology; phosphoprotein phosphatase; phosphorylation; predoctoral investigator; site directed mutagenesis; synapses

DESCRIPTION (provided by applicant): While learning and memory have mystified people for centuries, a cellular model for these processes eluded scientists until the discovery of LTP and LTD in the 1970s. Three decades later a general biochemical cascade involving calcium/calmodulin-dependent kinase II (CaMKII), protein phosphatase 1 (PP-1), and inhibitor-1 has gained widespread acceptance, although many details remain obscure. This proposal will employ biochemical and neuropharmacological techniques to characterize a novel phosphorylation event on inhibitor-1 by cyclin-dependent kinase 5 (Cdk5) and its implications for synaptic plasticity. The kinetics of this phosphorylation reaction and its effect upon inhibitor-1 activation, deactivation, and inhibitory activity against PP-1 will be assessed. Hippocampal slices will then be used to characterize this event in vivo, in terms of basal levels of phosphorylation, as well as modulation by different signaling pathways and possible effects on downstream PP-1 targets. Finally, the phosphatase(s) responsible for dephosphorylation of this site will be determined by both in vitro and in vivo methods.

描述（由申请人提供）：几个世纪以来，学习和记忆一直让人们感到困惑，但直到 20 世纪 70 年代 LTP 和 LTD 被发现之前，科学家们一直未能找到这些过程的细胞模型。三十年后，涉及钙/钙调蛋白依赖性激酶 II (CaMKII)、蛋白磷酸酶 1 (PP-1) 和抑制剂 1 的一般生化级联已获得广泛接受，尽管许多细节仍不清楚。该提案将采用生化和神经药理学技术来表征细胞周期蛋白依赖性激酶 5 (Cdk5) 对抑制剂 1 的新型磷酸化事件及其对突触可塑性的影响。将评估该磷酸化反应的动力学及其对inhibitor-1激活、失活和针对PP-1的抑制活性的影响。然后，海马切片将用于根据磷酸化的基础水平、不同信号通路的调节以及对下游 PP-1 靶标的可能影响来表征这一体内事件。最后，负责该位点去磷酸化的磷酸酶将通过体外和体内方法确定。