MYOSIN & THE REGULATION OF SMOOTH MUSCLE

平滑的肌肉对于维持所有脊索的动态平衡是必不可少的 动物。在人类中，平滑肌收缩反应中的异常 与高血压、心血管疾病和哮喘有牵连。 血管平滑肌功能的细胞和分子基础的阐明 因此，对许多病理生理学疾病的治疗至关重要 流程。现在人们普遍认为，Smooth的磷酸化 钙/钙调蛋白依赖酶肌球蛋白轻链的肌球蛋白 激酶是收缩过程中的一个关键调节事件。因此， 本提案中描述的实验旨在获得 详细了解肌球蛋白的作用 调节平滑肌的磷酸化/去磷酸化。 为了做到这一点，提出了三个系列的实验。在第一个 第二，我们将结合使用生理学、药理学和 研究平滑肌收缩的生化方法。我们有 在过去广泛使用了这些技术，这种方法已经 产生了一些重要的论文。 第三系列实验对PI来说是一个实质性的偏离 根据他以前的经验。在这个实验中，我们建议使用 研究平滑肌肉的分子生物学技术。因此，资金 由RCDA提供的将用于限制PI的教学和其他 部门职责，这样他就可以通过 与Rex Chisholm博士发展持续的合作，他是一位 分子生物学，肌球蛋白轻链的结构和功能。AS 他在分子生物学技术方面的经验增加了，PI将 将这项技术转移到他自己的实验室，并将其应用于研究 平滑的肌肉。 因此，PI的背景和专业知识将在一个重要的 在资助期内的纪律。此外，它的应用还包括 用分子生物学技术研究肌肉的生理学 结果详细地理解了肌球蛋白磷酸化在 平滑的肌肉，希望能改善平滑的治疗 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.