MECHANISM OF SHORTTERM REGULATION OF RENAL NA+/K+ ATPASE

肾NA/KATP酶的短期调节机制

• 批准号: 2518585
• 负责人: CARLOS H PEDEMONTE
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518585
• 关键词: enzyme activity; phorbols; phosphorylation; protein kinase C; site directed mutagenesis; sodium potassium exchanging ATPase

DESCRIPTION (taken in part from the application's abstract) The proposed studies are designed to address the hypothesis that the NH4-terminal segment of the alpha-subunit of the Na-K-ATPase interacts with other cytoplasmic domains of the same subunit to modulate enzyme activity. Site-directed mutagenesis will be used to identify amino acids that are phosphorylated by protein kinase C (PKC); phorbol 12-myristate 13-acetate (PMA) stimulation has been shown to increase the affinity of the enzyme for intracellular Na (sodium), presumably via PKC phosphorylation. Cross-linking reagents will be used to identify cytoplasmic domains that interact with the NH-terminus of the alpha-subunit. The effect of phosphorylation on partial reactions of the Na-K-ATPase will be determined to attempt to define mechanisms of hormonal regulation of the enzyme. The ultimate aim is to understand molecular mechanisms of action of the Na-K-ATPase and thereby define pathophysiology of cardiovascular diseases potentially caused by dysfunction of this critical enzyme.

描述（部分摘自申请摘要） 拟议的研究旨在解决假设， Na-K-ATP酶α亚基的NH 4-末端片段与 相同亚基的其他胞质结构域来调节酶活性。 将使用定点诱变来鉴定与突变相关的氨基酸。 被蛋白激酶C磷酸化;佛波醇12-肉豆蔻酸酯13-乙酸酯 (PMA)刺激已显示出增加酶的亲和力， 细胞内Na（钠），推测通过PKC磷酸化。 交联试剂将用于鉴定细胞质结构域， 与α亚基的NH末端相互作用。 的影响 将确定Na-K-ATP酶部分反应的磷酸化作用 试图确定酶的激素调节机制。 的 最终的目的是了解分子机制的行动， Na-K-ATP酶，从而定义心血管疾病的病理生理学 可能是由这种关键酶的功能障碍引起的。