REGULATION OF PROTEIN KINASES AND THEIR SUBSTRATES

蛋白激酶是一种重要的调节酶，在细胞水平上参与控制几乎所有的生理过程。人类基因组被认为含有大约1500个蛋白激酶来控制这些过程。这些酶将磷酸基团添加到目标蛋白质上，以可逆的方式改变其功能，蛋白质磷酸酶去除磷酸基团。本项目致力于研究一种代谢性应激敏感蛋白激酶，称为AMP激活蛋白激酶及其底物。在高能量需求时期，如剧烈运动或饥饿或缺血引起的营养应激，AMP激活的蛋白激酶负责关闭能量，需要代谢途径，并加速代谢，包括葡萄糖摄取和脂肪酸代谢，以恢复细胞能量水平。AMP激活的蛋白激酶调节控制胆固醇和脂肪(脂肪酸)合成的关键酶，以及内皮型一氧化氮合酶，后者是血压和血小板活性的关键调节因子。出于这些原因，它在心血管疾病中具有潜在的重要意义。AMP激活的蛋白激酶似乎也与运动诱导的葡萄糖摄取有关，众所周知，运动有助于恢复发病年龄或II型糖尿病患者的血糖控制。由于AMP激活的蛋白激酶加速脂肪酸代谢，它也可能在肥胖中发挥作用。虽然许多因素被认为与心血管疾病、糖尿病和肥胖症有关，但AMP激活的蛋白激酶是与澳大利亚最重要的疾病相关的关键代谢调节酶。了解AMP激活的蛋白激酶的结构和功能以及编码该酶的基因是一个重要的目标。

Protein kinases are important regulatory enzymes involved in the control of virtually all physiological processes at the cellular level. The human genome is thought to contain approximately 1500 protein kinases to control these processes. These enzymes add phosphate groups to target proteins to modify their functions in a reversible manner with protein phosphatases removing the phosphate groups. This project is concerned with studying a metabolic stress sensing protein kinase called the AMP activated protein kinase and its substrates. During periods of high energy demand such as vigorous exercise or nutrient stress induced by starvation or ischaemia the AMP activated protein kinase is responsible for shutting down energy requiring metabolic pathways and accelerating metabolism including glucose uptake and fatty acid metabolism to restore cellular energy levels. The AMP activated protein kinase regulates key enzymes in the control of cholesterol and lipid (fatty acid) synthesis as well as endothelial NO synthase, a key regulator of blood pressure and platelet activity. For these reasons it is potentially important in cardiovascular disease. The AMP activated protein kinase also appears responsible for exercise induced glucose uptake and it is known that exercise helps restore glucose control in age onset or type II diabetic patients. Since the AMP acitivated protein kinase accelerates fatty acid metabolism it may also have a role in obesity. While many factors are thought to be involved in cardiovascular disease, diabetes and obesity the AMP activated protein kinase is a key metabolic regulatory enzyme relevant to the most important diseases in Australia. Understanding the structure and function of the AMP activated protein kinase as well as the genes that encode this enzyme is an important goal.