Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A
Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A
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DOI：
10.1073/pnas.220413597
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发表时间：
2000-10-24
影响因子：
11.1
通讯作者：
Mills, GB
中科院分区：
文献类型：
--
作者：
Fang, XJ;Yu, SX;Mills, GB
糖原合成酶激酶3（GSK-3）参与多种生物学过程，包括代谢、基因表达、细胞命运决定、增殖和存活。GSK-3活性通过GSK-3 α中的丝氨酸21和GSK-3 β中的丝氨酸蛋白的磷酸化而被抑制。GSK-3的这些丝氨酸残基先前已被鉴定为蛋白激酶B（PKB/Akt）的靶标，PKB是一种位于磷脂酰肌醇3-激酶下游的丝氨酸/苏氨酸激酶。我们发现GSK-3 α中的丝氨酸21和GSK-3 β中的丝氨酸9也是cAMP依赖性蛋白激酶A的生理底物。蛋白激酶A与GSK-3的两种同种型物理结合、磷酸化和失活。结果表明，根据刺激的背景下，GSK-3的活性可以调制通过磷脂酰肌醇3-激酶-蛋白激酶级联或G蛋白偶联受体的激素刺激，连接到细胞内cAMP水平的变化的生长因子的工作。
Glycogen synthase kinase 3 (GSK-3) is implicated in multiple biological processes including metabolism, gene expression, cell fate determination, proliferation, and survival. GSK-3 activity is inhibited through phosphorylation of serine 21 in GSK-3 alpha and serine gin GSK-3 beta, These serine residues of GSK-3 have been previously identified as targets of protein kinase B (PKB/Akt), a serine/threonine kinase located downstream of phosphatidylinositol 3-kinase, Here, we show that serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta are also physiological substrates of cAMP-dependent protein kinase A. Protein kinase A physically associates with, phosphorylates, and inactivates both isoforms of GSK-3. The results indicate that depending on the stimulatory context, the activity of GSK-3 can be modulated either by growth factors that work through the phosphatidylinositol 3-kinase-protein kinase a cascade or by hormonal stimulation of G protein-coupled receptors that link to changes in intracellular cAMP levels.