Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B.
Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B.
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DOI：
10.1042/bj2940625
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发表时间：
1993-09
期刊：
影响因子：
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通讯作者：
G. Welsh;C. Proud
中科院分区：
文献类型：
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作者：
G. Welsh;C. Proud
我们研究了转染人胰岛素受体（CHO.T 细胞）的中国仓鼠卵巢细胞中胰岛素调节蛋白激酶的控制。这些酶中有一种是在 Mono-S 上对细胞提取物进行层析后获得的，其活性在胰岛素处理 10 分钟内降低（7.3 +/- 1.9 倍）。该酶磷酸化糖原合酶和蛋白质合成真核起始因子 (eIF)-2B（鸟嘌呤核苷酸交换因子）的最大亚基。该激酶似乎是糖原合酶激酶 3 (GSK-3)，基于：(1) 其能够根据糖原合酶中 GSK-3 的磷酸化位点磷酸化肽，以及 (2) 发现具有此活性的级分含有免疫反应性 GSK-3，其峰值与激酶活性的峰值一致，如通过以下判断的 使用 GSK-3 α 和 β 异构体特异性抗体进行免疫印迹。用蛋白磷酸酶-2A 处理柱级分可逆转胰岛素诱导的激酶活性降低。这些数据表明胰岛素迅速导致 GSK-3 失活，这是由于 GSK-3 磷酸化所致。讨论了这些发现对糖原和蛋白质代谢控制的影响。
We have studied the control of insulin-regulated protein kinases in Chinese hamster ovary cells transfected with the human insulin receptor (CHO.T cells). Among these enzymes is one that is obtained after chromatography of cell extracts on Mono-S, whose activity is decreased (7.3 +/- 1.9-fold) within 10 min of insulin treatment. This enzyme phosphorylates glycogen synthase and the largest subunit of protein synthesis eukaryotic initiation factor (eIF)-2B (the guanine nucleotide exchange factor). The kinase appears to be glycogen synthase kinase-3 (GSK-3), on the basis of: (1) its ability to phosphorylate a peptide based on the phosphorylation sites for GSK-3 in glycogen synthase, and (2) the finding that the fractions possessing this activity contain immunoreactive GSK-3, whose peak is coincident with that of kinase activity, as judged by immunoblotting using antibodies specific for the alpha- and beta-isoforms of GSK-3. The decrease in kinase activity induced by insulin was reversed by treatment of the column fractions with protein phosphatase-2A. These data indicate that insulin rapidly causes inactivation of GSK-3 and that this is due to phosphorylation of GSK-3. The implications of these findings for the control of glycogen and protein metabolism are discussed.