A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta.
A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta.
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A 激酶锚定蛋白 AKAP220 与糖原合酶激酶激酶 3beta (GSK-3beta) 结合并介导 GSK-3beta 的蛋白激酶 A 依赖性抑制。
DOI：
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发表时间：
2002
影响因子：
4.8
通讯作者：
A. Kikuchi
中科院分区：
文献类型：
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作者：
C. Tanji;Hideki Yamamoto;N. Yorioka;N. Kohno;K. Kikuchi;A. Kikuchi
糖原合成酶激酶3 （GSK-3）受多种细胞外配体调控，磷酸化多种底物，从而调节细胞功能。通过酵母双杂交筛选，我们发现GSK-3beta与AKAP220结合，而AKAP220是一种已知的a激酶锚定蛋白。gsk -3 β在完整细胞内源性水平上与AKAP220形成复合物。在该复合物中还检测到环amp依赖性蛋白激酶（PKA）和1型蛋白磷酸酶（PP1），表明AKAP220、gsk -3 β、PKA和PP1形成了一个四元复合物。据报道，PKA使gsk -3 β磷酸化，从而降低其活性。用二丁基环AMP活化COS细胞后，与AKAP220结合的gsk -3 β活性比gsk -3 β总活性下降更明显。蛋白磷酸酶抑制剂Calyculin A对gsk -3 β与AKAP220结合活性的抑制作用强于对gsk -3 β总活性的抑制作用。这些结果表明，PKA和PP1通过与AKAP220形成复合物有效调节gsk -3 β的活性。
Glycogen synthase kinase-3 (GSK-3) is regulated by various extracellular ligands and phosphorylates many substrates, thereby regulating cellular functions. Using yeast two-hybrid screening, we found that GSK-3beta binds to AKAP220, which is known to act as an A-kinase anchoring protein. GSK-3beta formed a complex with AKAP220 in intact cells at the endogenous level. Cyclic AMP-dependent protein kinase (PKA) and type 1 protein phosphatase (PP1) were also detected in this complex, suggesting that AKAP220, GSK-3beta, PKA, and PP1 form a quaternary complex. It has been reported that PKA phosphorylates GSK-3beta, thereby decreasing its activity. When COS cells were treated with dibutyryl cyclic AMP to activate PKA, the activity of GSK-3beta bound to AKAP220 decreased more markedly than the total GSK-3beta activity. Calyculin A, a protein phosphatase inhibitor, also inhibited the activity of GSK-3beta bound to AKAP220 more strongly than the total GSK-3beta activity. These results suggest that PKA and PP1 regulate the activity of GSK-3beta efficiently by forming a complex with AKAP220.