REGULATION OF CALMODULIN-DEPENDENT PROTEIN KINASES

钙调蛋白依赖性蛋白激酶的调节

• 批准号: 2265346
• 负责人: ARTHUR M EDELMAN
• 金额: $ 13.39万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265346
• 关键词: animal tissue; calcium flux; calmodulin dependent protein kinase; enzyme activity; isozymes; laboratory rat; phosphorylation; protein purification; protein sequence

The long-term objective of this research is to understand the biological role of Ca2+-dependent protein phosphorylation. Increased intracellular Ca2+ generated by cell stimulation is known to regulate a broad range of cellular events such as egg fertilization, secretion, muscle contraction, gene expression and many others. One pivotal class of mediators of the effects of Ca2+ are Ca2+-dependent protein kinases, the majority of which are dependent for their activity upon Ca2+ complexed with calmodulin (CaM). The impetus for this research is the discovery of two novel CaM-dependent protein kinases, CaM kinases Ia and Ib, and the finding that they are themselves regulated by phosphorylation. Definition of the mechanisms by which CaM kinase Ia and lb are regulated is likely to aid in the identification of extracellular signals acting in concert with those regulating intracellular Ca2+ to control cellular function. Since the proteins involved in this regulation, CaM kinase Ia activators and CaM kinase lb kinase may be newly discovered they have the potential to participate in the regulation of other cellular activities and therefore be of broad biological significance. A recent report suggests a potential role for CaM kinases Ia and lb in the pathogenesis of Alzheimer's disease. The specific aims of this project are: Specific Aim l: Purification and characterization of proteins which regulate CaM kinase Ia and CaM kinase Ib. The main objectives are to determine if CaM kinase Ia activators and CaM kinase Ib kinase are previously unrecognized proteins. Specific Aim 2: Mechanisms for the regulation of CaM kinase Ia and Ib. The main objectives are to understand the role of phosphorylation in the activation of CaM kinases Ia and Ib and to determine if CaM kinase Ia activators and CaM kinase Ib kinase are also regulated by phosphorylation.

这项研究的长期目标是了解生物学 Ca2+依赖性蛋白磷酸化的作用。 已知通过细胞刺激产生的细胞内Ca2+增加 调节广泛的细胞事件，例如卵受精， 分泌，肌肉收缩，基因表达以及许多其他。 一 Ca2+效应的介体的关键类别是Ca2+依赖性的 蛋白激酶，其中大多数取决于其活性 在Ca2+与钙调蛋白（CAM）复合的情况下。这项研究的动力 是发现两个新型CAM依赖性蛋白激酶的发现CAM激酶 ia和ib，以及他们本身受到的发现 磷酸化。 CAM激酶IA和 LB受调节可能有助于鉴定细胞外 与调节细胞内Ca2+的信号一起作用 控制细胞功能。 由于蛋白质涉及 调节，CAM激酶IA激活剂和CAM激酶LB激酶可能是新的 发现他们有可能参与 其他细胞活动，因此具有广泛的生物学 意义。 最近的一份报告表明CAM激酶的潜在作用 IA和LB在阿尔茨海默氏病的发病机理中。 该项目的具体目的是：特定目标L：净化和 调节CAM激酶IA和CAM激酶的蛋白质的表征 IB。 主要目标是确定CAM激酶IA激活剂和 CAM激酶IB激酶以前是未识别的蛋白质。 具体目标 2：调节CAM激酶IA和IB的机制。 主 目标是了解磷酸化在激活中的作用 CAM激酶IA和IB的CAM激酶，并确定CAM激酶IA激活剂和是否是否 CAM激酶IB激酶也受磷酸化调节。