HORMONAL REGULATION OF CELLULAR METABOLISM

控制限速酶的磷酸化-去磷化 步骤是细胞新陈代谢最重要的机制之一 由荷尔蒙和其他调节剂控制。糖原合成酶和 磷酸化酶是受这种机制调节的两种酶。 对荷尔蒙的反应。这些酶可以被磷酸化并 分别由多种形式的蛋白激酶和蛋白激酶去磷酸化 磷酸酶。目前还不完全清楚荷尔蒙如何影响 各种蛋白激酶和磷酸酶的活性。上一首 研究已经确定了胰升糖素和β-肾上腺素能激动剂的作用 通过cAMP和cAMP依赖的蛋白激酶途径。 然而，其他激素介导的磷酸化系统的作用 尚未与某些激酶的作用直接相关。 促进肿瘤的佛波醇酯模仿某些激素的作用，这些激素 调节分离的肝细胞的糖原合成酶活性。这个 这些佛波醇酯引起的多效性反应可能是 通过结合和激活它们的受体，这已经被 初步鉴定为磷脂依赖和钙激活 蛋白激酶(蛋白激酶C)。这种蛋白激酶普遍存在于 真核生物，并似乎在调解的行动中发挥关键作用 信号诱导肌醇磷脂的分解。蛋白激酶C来自 大鼠的大脑已经被高产率地提纯到接近均一的水平。这 酶使糖原合成酶磷酸化，而不会导致其失活， 与将完整的肝细胞暴露于 促进肿瘤的光酚酸酯。这些发现表明，这些行动 除蛋白激酶C外，还必须有其他介质的参与 表达佛波醇酯的效果。多克隆和单克隆 针对蛋白激酶C的抗体已经准备好用于 免疫细胞化学研究和蛋白激酶C的调节 通过自动磷酸化的活性正在调查中。

Phosphorylation-dehosphorylation of enzymes controlling rate-limiting steps is one of the most important mechanisms by which cellular metabolism is controlled by hormones and other regulators. Glycogen synthase and phosphorylase kinase are two of such enzymes regulated by this mechanism in response to hormonal actions. These enzymes can be phosphorylated and dephosphorylated, respectively, by multiple forms of protein kinases and phosphatases. It is not entirely understood how hormones affect the activities of the various protein kinases and phosphatases. Previous studies have defined the action of glucagon and Beta-adrenergic agonists via the pathway involving cAMP and cAMP-dependent protein kinase. However, the actions of other hormone-mediated phosphorylation systems have yet to be correlated directly with the action of certain kinases. Tumor-promoting phorbol esters mimic the action of some hormones which regulate glycogen synthase activity in isolated hepatocytes. The pleiotropic responses elicited by these phorbol esters are presumably through binding and activation of their receptor, which has been tentatively identified as a phospholipid-dependent and calcium-activated protein kinase (protein kinase C). This protein kinase is ubiquitous in eukaryotes and seems to play a pivotal role in mediating the actions of signal-induced breakdown of inositol phospholipids. Protein kinase C from rat brain has been purified to near homogeneity in high yield. This enzyme phosphorylates glycogen synthase without causing its inactivation, in contrast to the effect of exposing intact hepatocytes to tumor-promoting phobol esters. These findings indicate that the actions of other mediators in addition to protein kinase C must be necessary to express the effect of phorbol esters. Polyclonal and monoclonal antibodies against protein kinase C have been prepared for immunocytochemical studies, and the regulation of protein kinase C activity by autophosphorylation is under investigation.