Regulation of Serine/Threonine Kinase in Skeletal Muscle

骨骼肌中丝氨酸/苏氨酸激酶的调节

• 批准号: 6773583
• 负责人: LAURIE J GOODYEAR
• 金额: $ 39.48万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6773583
• 关键词: biological signal transduction; cadherins; enzyme activity; exercise; genetically modified animals; glucose transport; glycogen synthase; insulin; laboratory mouse; laboratory rat; muscle contraction; muscle metabolism; phosphatidylinositol 3 kinase; phosphorylation; serine threonine protein kinase; striated muscles

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.

描述(由申请人提供)：体育锻炼能显著增加骨骼肌对葡萄糖的摄取，在运动后的一段时间内，葡萄糖摄取和糖原合成的速率都会增加。单次运动还会导致基因转录的瞬时变化和蛋白质代谢的改变，这两点对于反复运动后观察到的慢性适应都很重要。骨骼肌的这些适应能力导致了运动对健康的一些最重要的好处，可能包括定期体育锻炼降低患2型糖尿病的风险。运动生物学中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机制。我们已经证实，运动调节骨骼肌中的Akt和GSK3信号，这两个关键的丝氨酸/苏氨酸(Ser/Thr)蛋白激酶参与了一系列细胞代谢和转录事件的调节。为了了解这些蛋白在收缩骨骼肌中的生理功能，人们提出了4个具体的目标：1)阐明运动引起Akt激活的信号机制，并确定运动诱导的Akt激活的生物学后果；2)阐明运动降低骨骼肌GSK3活性的机制；3)确定运动诱导骨骼肌GSK3失活的生物学后果；4)确定运动对骨骼肌GSK3表达和活性的影响。这项工作应该有助于更好地理解运动对骨骼肌有益影响的分子信号机制。