INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B
INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B
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DOI：
10.1038/378785a0
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发表时间：
1995-12-21
期刊：
影响因子：
64.8
通讯作者：
HEMMINGS, BA
中科院分区：
文献类型：
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作者：
CROSS, DAE;ALESSI, DR;HEMMINGS, BA
糖原合成酶激酶-3（GSK 3）（1）参与调节多种生理过程，包括胰岛素对糖原（2）和蛋白质（3）合成的控制、转录因子AP-1和CREB（4-6）的调节、果蝇细胞命运的特化（7）和非洲爪蟾胚胎的背腹图案化（8）。GSK 3在体外可被响应胰岛素或生长因子的丝氨酸磷酸化抑制，并被MAP激酶活化蛋白（MAPKAP）激酶-1（也称为p90（rsk））或p70核糖体S6激酶（p70（S6 k））抑制（12，13）。然而，在这里，我们表明，在体内阻止胰岛素激活MAPKAP激酶-1和p70（S6 k）的药物并不阻断GSK 3的磷酸化和抑制。另一种胰岛素刺激的蛋白激酶在这些条件下使GSK 3失活，Ne证明它是原癌基因蛋白激酶B（PK B，也称为Akt/RAC）的产物。与GSK 3的抑制作用一样（参考文献10、14），PKB的激活也可通过磷脂酰肌醇（PT）3-激酶抑制剂来阻止。
GLYCOGEN synthase kinase-3 (GSK3)(1) is implicated in the regulation of several physiological processes, including the control of glycogen(2) and protein(3) synthesis by insulin, modulation of the transcription factors AP-1 and CREB(4-6), the specification of cell fate in Drosophila(7) and dorsoventral patterning in Xenopus embryos(8). GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90(rsk)) or p70 ribosomal S6 kinase (p70(S6k))(12,13). Here we show, however, that agents which prevent the activation of both MAPKAP kinase-1 and p70(S6k) by insulin in vivo do not block the phosphorylation and inhibition of GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and Ne demonstrate that it is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PT) 3-kinase.