ACTIVATION OF PROTEIN KINASE C

蛋白激酶 C 的激活

• 批准号: 2701741
• 负责人: MICHAEL GLASER
• 金额: $ 19.5万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2701741
• 关键词: actin binding protein; biological signal transduction; calcium; chemical kinetics; diacylglycerols; digital imaging; enzyme activity; enzyme mechanism; enzyme substrate; fatty acylation; fluorescence microscopy; lipid bilayer membrane; membrane activity; membrane lipids; membrane reconstitution /synthesis; membrane structure; myristates; phosphatidylserines; phosphorylation; protein kinase C; stoichiometry

One of the central questions in biology is to understand how cells communicate with their environment and the mechanism of signal transduction. Membranes play an essential role in this as well as many other cellular phenomena. The major objective of this research is to determine the role of lipid domains in activating protein kinase C. The development of fluorescence digital imaging microscopy has allowed the direct measurement of the lateral distribution of phospholipids in unilamellar vesicles and the red blood cell membrane. The results suggest a model of membrane structure with a heterogeneous distribution of lipid components that can change in response to a variety of agents such as calcium. It is proposed that lipid domains have an important role in a variety of membrane functions such as the activation of protein kinase C and signal transduction across membranes. Several external stimuli, such as hormones and growth factors, can cause the increased production of diacylglycerol in the plasma membrane and diacylglycerol acts as a second messenger to activate protein kinase C. Calcium and phosphatidylserine are also necessary for this process. Fluorescence digital imaging microscopy will be used to study the structure and organization of the membrane complex between protein kinase C, membrane lipids, calcium, and the substrates of protein kinase C phosphorylation under conditions that lead to enzyme activation. If the components are concentrated or ordered in a domain, this would greatly increase the reaction rate. This research also should help determine if factors that modulate the reaction interact directly with the enzyme or alter the nature of the membrane complex. Interactions between the two leaflets of the bilayer and the subsequent effect on the organization of the reaction components will be investigated as a mechanism for transmembrane signalling. It seems reasonable that many components of signal transduction pathways would show some organization into membrane domains since this would significantly increase the specificity and efficiency of the signal transduction process. It is proposed that the information obtained from these studies on protein kinase C will be of general significance for the lateral organization of membranes and signal transduction s well as for understanding the pathogenesis of membrane-related disease processes.

生物学的核心问题之一是了解细胞如何 与他们的环境和信号机制进行沟通 转导。 膜在这方面起着至关重要的作用 其他细胞现象。 这项研究的主要目的是 确定脂质结构域在激活蛋白激酶C中的作用。 荧光数字成像显微镜的开发允许 直接测量磷脂中磷脂的横向分布 单层囊泡和红细胞膜。 结果表明 具有脂质异质分布的膜结构模型 可以响应各种代理的组件，例如 钙。 有人提出脂质结构域在 多种膜功能，例如蛋白激酶C的激活 和跨膜的信号转导。 几种外部刺激 作为激素和生长因素，可能导致增加 质膜中的二酰基甘油和二酰基甘油充当第二 激活蛋白激酶C.钙和磷脂酰丝氨酸的信使是 对于此过程也是必要的。 荧光数字成像显微镜 将用于研究膜的结构和组织 蛋白激酶C，膜脂质，钙和钙之间的复合物与 在铅的条件下，蛋白激酶C磷酸化的底物 激活酶。 如果组件集中或在 域，这将大大提高反应率。 这项研究也是如此 应该有助于确定调节反应的因素是否相互作用 直接使用酶或改变膜络合物的性质。 双层的两个传单与后续的相互作用 将研究对反应组件组织的影响 作为跨膜信号传导的机制。 许多信号转导途径的许多组件似乎是合理的 会向膜域展示一些组织，因为这将 显着提高信号的特异性和效率 转导过程。 建议从 这些关于蛋白激酶C的研究对 膜和信号转导的横向组织以及 了解与膜相关疾病过程的发病机理。