MYOSIN & THE REGULATION OF SMOOTH MUSCLE

平滑肌对于维持所有脊索动物的内环境平衡是必不可少的 动物在人类中，平滑肌收缩反应的畸变 与高血压心血管疾病和哮喘有关。 阐明平滑肌功能的细胞和分子基础 因此，对于治疗许多病理生理性疾病至关重要。 流程.现在普遍认为， 钙/钙调蛋白依赖性肌球蛋白轻链 激酶是收缩过程中的关键调节事件。因此，委员会认为， 本提案中描述的实验旨在获得 详细了解肌球蛋白的作用 磷酸化/去磷酸化N调节平滑肌。 为了做到这一点，提出了三个系列的实验。上 第二，我们将使用生理学、药理学和 研究平滑肌收缩的生物化学方法。我们有 在过去广泛使用这些技术，这种方法 产生了一些重要的论文。 第三系列实验代表了PI的实质性偏离 从他以前的经验。在这个实验中，我们建议使用 分子生物学技术来研究平滑肌。因此，资金 由RCDA提供的将被用来削减PI的教学和其他 部门的职责，以便他可以学习分子生物学， 发展与雷克斯奇泽姆博士的持续合作， 分子生物学，肌球蛋白轻链的结构和功能。作为 他在分子生物学技术方面的经验增加，PI将 把这项技术转移到他自己的实验室， 平滑肌 因此，PI的背景和专业知识将在一个重要的 在融资过程中的纪律此外，应用 研究平滑肌生理学的分子生物学技术将 导致详细了解肌球蛋白磷酸化在 平滑肌，希望能改善平滑肌的治疗， 肌肉相关疾病

Smooth muscles are essential for maintaining homeostasis in all chordate animals. In humans, aberrations in smooth muscle contractile responses have been implicated in hypertension, cardiovascular disease and asthma. Elucidation of the cellular and molecular basis of smooth muscle function is, therefore, crucial for the therapy of a number pathophysiological processes. It is now generally accepted that the phosphorylation of smooth muscle myosin by the Ca 2+/calmodulin dependent enzyme myosin light chain kinase is a key regulatory event in the contractile process. Consequently, the experiments described in this proposal are designed to obtain a detailed understanding of the role of myosin phosphorylation/dephosphorylation n regulating smooth muscles. Three series of experiments are proposed in order to do so. In the first two, we will use a combination of physiological, pharmacological and biochemical approaches to investigate smooth muscle contraction. We have used these techniques extensively in the past and this approach has resulted in a number of important papers. The third series of experiments represents a substantial departure for PI from his previous experience. In this experiment we propose to use molecular biology techniques to study smooth muscles. Therefore, funds provided by the RCDA will be used to curtail the PI's teaching and other departmental responsibilities so that he can learn molecular biology by developing an ongoing collaboration with Dr. Rex Chisholm, an expert in molecular biology, on the structure and function of myosin light chains. As his experience with molecular biology techniques increases, the PI will transfer this technology to his own laboratory and apply them to the study of smooth muscle. Thus, the PI's background and expertise will increase in an important discipline during the funding period. Moreover, the application of molecular biology techniques to study the physiology of smooth muscles will result in a detailed understanding of the role of myosin phosphorylation in smooth muscles and, hopefully, improved therapy for smooth muscle-associated diseases.