Early protein kinase and biosynthetic responses to insulin.
Early protein kinase and biosynthetic responses to insulin.
复制标题
早期蛋白激酶和对胰岛素的生物合成反应。
DOI：
10.1042/bst0200682
复制
发表时间：
1992
影响因子：
3.9
通讯作者：
Blackshear,PJ
中科院分区：
文献类型：
--
作者：
Blackshear,PJ
胰岛素作用的分子机制仍然是一个有趣的和未解决的生物学难题。这个难题值得解决，因为它的内在生物学利益，但也因为其明显的临床相关性，胰岛素抵抗的常见状态，如I1型糖尿病和肥胖症。在这些疾病中，胰岛素抵抗似乎发生在“受体后”位点，因为胰岛素受体的一级结构及其内在酪氨酸蛋白激酶活性似乎是正常的。因此，研究胰岛素的受体后作用的一个目的。了解胰岛素占据其受体后发生的一系列完整反应以及随后的细胞内效应;一旦在分子水平上理解了这些反应，就有可能确定胰岛素抵抗状态中的缺陷位点，研究胰岛素受体后作用的另一个理由是，事实上，胰岛素代表一类生长因子，还包括胰岛素样生长因子I和集落刺激因子1，其作用似乎不受肌醇或胆碱磷脂水解的快速刺激介导。通过激活磷脂酶C或D刺激这些磷脂的分解代表了许多其他生长因子以及许多种类的药物、神经递质和激素所采用的非常常见的信号转导模式。然而，这些激动剂中的许多，特别是生长因子如血小板衍生生长因子或表皮生长因子（EGF），也可以通过明显不依赖于磷脂酶C或D活化的机制作用于细胞。因此，我们将胰岛素信号传导机制的研究视为许多其他生长因子和激素的非磷脂酶依赖性作用的范例。
The molecular mechanism of insulin action remains an intriguing and unsolved biological puzzle. This puzzle deserves to be solved because of its intrinsic biological interest, but also because of its obvious clinical relevance to common states of insulin resistance such as Type I1 diabetes and obesity. In these disorders, the insulin resistance appears to occur at a ‘post-receptor’locus, in that the primary structure of the insulin receptor, and its intrinsic tyrosine protein kinase activity, appear to be normal. One object of studying the post-receptor actions of insulin, therefore. is to understand the complete series of reactions that occur after insulin occupancy of its receptor and a subsequent intracellular effect; once these reactions are understood at the molecular level, then it might be possible to determine the locus of the defect in states of insulin resistance, and eventually to design specific therapies directed at correcting this defect.Another justification for studying the postreceptor actions of insulin derives from the fact that insulin represents a class of growth factors, which also includes insulin-like growth factor I and colony-stimulating factor 1, whose actions do not appear to be mediated by the rapid stimulation of inositol or choline phospholipid hydrolysis. Stimulation of the breakdown of these phospholipids through the activation of phospholipase C or D represents a very common mode of signal transduction that is employed by numerous other growth factors, as well as by many classes of drugs, neurotransmitters and hormones. I Iowever, many of these agonists, in particular growth factors such as platelet-derived growth factor or epidermal growth factor (EGF), can also act on cells through mechanisms apparently independent of phospholipase C or D activation. We therefore view the study of insulin’s mechanism of signal transduction as a paradigm for the phospholipase-independent effects of a number of other growth factors and hormones.