PHOSPHORYLATION OF CALPAINS

钙蛋白酶的磷酸化

• 批准号: 7957763
• 负责人: DARREL E GOLL
• 金额: $ 0.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957763
• 关键词: Alzheimer' s Disease; Area; Biology; Blood Vessels; Calpain; Cataract; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; Crystallins; Event; Funding; Fungal Genome; Genes; Goals; Grant; Institution; Learning; Life; Muscular Dystrophies; Myocardial Infarction; Normal Cell; Pathology; Peptide Hydrolases; Phosphorylation; Regulation; Research; Research Personnel; Research Project Grants; Resources; Site; Source; Spinal cord injury; Stroke; Tissues; United States National Institutes of Health; in vitro Assay; m-calpain; muscle form

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. The long-term goal of this research is to learn how activity of the ubiquitous calpains, ¿- and m-calpain, is regulated in living cells. The calpains are Ca2+-dependent proteases found in every vertebrate cell. Disruption of the gene encoding the 28-kDa subunit common to ¿- and m-calpain is embryonically lethal. Inappropriate calpain degradation is implicated in many tissue pathologies ranging from loss of muscle mass in the muscular dystrophies, to crystallin degradation and cataract formation, to Alzheimer?s disease, to tissue damage in ischemic areas near a blocked blood vessel (stroke or myocardial infarction), to traumatic spinal cord injury, etc. Calpain activity in these pathologies is triggered by elevated, intracellular [Ca2+]; however, Ca2+ requirement of the calpains in in vitro assays is 3-50 ¿M (¿-calpain) or 300-500 ¿M (m-calpain), much higher than intracellular free [Ca2+] is, even near ischemic areas. Cells, therefore, have a mechanism to reduce the [Ca2+] required for calpain activity. This mechanism evidently is altered in a way that activates the calpains during ischemic events. The same mechanism must regulate calpain activity during normal cell function. We have found that both ¿- and m-calpain are phosphorylated at multiple sites. The objective of our current research project is to identify the phosphorylated sites on both ¿- and m-calpain and determine their effect on regulation of calpain activity.

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。 这项研究的长期目标是了解普遍存在的钙蛋白酶，钙蛋白酶和m-钙蛋白酶的活性如何在活细胞中调节。钙蛋白酶是在每种脊椎动物细胞中发现的钙依赖性蛋白酶。破坏编码<$-和m-钙蛋白酶共同的28-kDa亚基的基因是胚胎致死的。不适当的钙蛋白酶降解与许多组织病理学有关，从肌营养不良症中的肌肉质量损失，到晶体蛋白降解和白内障形成，再到阿尔茨海默病？s疾病，在阻塞血管附近的缺血区域的组织损伤这些病理中的钙蛋白酶活性由升高的细胞内[Ca 2 +]触发;然而，在体外测定中钙蛋白酶的Ca 2+需求为3-50 μ M。（<$-钙蛋白酶）或300-500 <$M（m-钙蛋白酶），远高于细胞内游离[Ca 2 +]，即使在缺血区附近。因此，细胞具有降低钙蛋白酶活性所需的[Ca 2 +]的机制。这一机制显然以在缺血事件期间激活钙蛋白酶的方式改变。在正常细胞功能期间，同样的机制必须调节钙蛋白酶活性。我们已经发现，无论是<$-calpain和m-calpain磷酸化在多个网站。我们目前的研究项目的目的是确定磷酸化位点的钙蛋白酶和m-钙蛋白酶，并确定其调节钙蛋白酶活性的影响。