Regulation of Serine/Threonine Kinase in Skeletal Muscle

描述（由申请人提供）：体育锻炼可急剧增加骨骼肌葡萄糖摄取，在运动后的一段时间内，葡萄糖摄取和糖原合成速率均增加。单次运动也会引起基因转录的短暂变化，并改变蛋白质代谢的速率，这两者对于反复运动后观察到的慢性适应都很重要。骨骼肌中的这些适应性变化导致了运动对健康的一些最重要的益处，可能包括定期体育锻炼降低患2型糖尿病风险的能力。运动生物学的一个中心问题是阐明调节骨骼肌中这些重要代谢和转录事件的分子信号传导机制。我们已经确定，运动调节骨骼肌中的Akt和GSK 3信号传导，这两种关键的丝氨酸/苏氨酸（Ser/Thr）蛋白激酶参与了许多细胞代谢和转录事件的调节。为了了解这些蛋白在骨骼肌收缩中的生理功能，提出了4个具体目标：1）阐明运动导致Akt激活的信号传导机制，并确定运动诱导的骨骼肌Akt激活的生物学后果; 2）阐明运动降低骨骼肌中GSK 3活性的机制; 3）确定骨骼肌中运动诱导的GSK 3失活的生物学后果;和4）确定运动训练对骨骼肌中GSK 3表达和活性的影响。这项工作应该导致更好地理解的分子信号机制负责的有益影响，体育锻炼骨骼肌。

DESCRIPTION (provided by applicant): Physical exercise acutely increases skeletal muscle glucose uptake, and in the period following exercise there are increases in the rates of both glucose uptake and glycogen synthesis. A single bout of exercise also induces transient changes in gene transcription and alters rates of protein metabolism, both of which are important for the chronic adaptations observed after repeated bouts of exercise. These adaptations in skeletal muscle lead to some of the most important health benefits of exercise, perhaps including the ability of regular physical exercise to reduce the risk of developing type 2 diabetes. A central issue in exercise biology is to elucidate the molecular signaling mechanisms that regulate these important metabolic and transcriptional events in skeletal muscle. We have established that exercise regulates Akt and GSK3 signaling in skeletal muscle, two critical serine/threonine (Ser/Thr) protein kinases that have been implicated in the regulation of a host of cellular metabolic and transcriptional events. To understand the physiological function of these proteins in contracting skeletal muscle 4 specific aims have been proposed: 1) to elucidate the signaling mechanism that leads to Akt activation with exercise, and to determine the biological consequences of exercise-induced activation of Akt in skeletal muscle; 2) to elucidate the mechanisms through which exercise decreases GSK3 activity in skeletal muscle; 3) to determine the biological consequences of exercise-induced deactivation of GSK3 in skeletal muscle; and 4) to determine the effects of exercise training on GSK3 expression and activity in skeletal muscle. This work should lead to a better understanding of the molecular signaling mechanisms responsible for the beneficial effects of physical exercise in skeletal muscle.