Acetylation negatively regulates glycogen phosphorylase by recruiting protein phosphatase 1.
Acetylation negatively regulates glycogen phosphorylase by recruiting protein phosphatase 1.
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DOI：
10.1016/j.cmet.2011.12.005
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发表时间：
2012-01-04
期刊：
影响因子：
29
通讯作者：
Guan KL
中科院分区：
文献类型：
--
作者：
Zhang T;Wang S;Lin Y;Xu W;Ye D;Xiong Y;Zhao S;Guan KL
糖原磷酸化酶（GP）催化糖原代谢中的限速步骤，在维持细胞和生物体葡萄糖稳态中起关键作用。GP是第一个发现其功能受可逆性蛋白磷酸化调节的蛋白质，其由磷酸化酶激酶（PhK）和蛋白磷酸酶1（PP 1）控制。在这里，我们报告，赖氨酸乙酰化负调节GP活性直接抑制酶活性和促进去磷酸化。GP Lys470的乙酰化增强了其与PP1底物靶向亚基GL和PP1的相互作用，从而促进GP去磷酸化和失活。我们发现GP乙酰化被葡萄糖和胰岛素刺激，被胰高血糖素抑制。我们的研究结果提供了复杂的经典GP和蛋白质乙酰化和磷酸化之间的功能性串扰的调节分子的见解。
Glycogen phosphorylase (GP) catalyzes the rate-limiting step in glycogen catabolism and plays a key role in maintaining cellular and organismal glucose homeostasis. GP is the first protein whose function was discovered to be regulated by reversible protein phosphorylation, which is controlled by phosphorylase kinase (PhK) and protein phosphatase 1 (PP1). Here, we report that lysine acetylation negatively regulates GP activity by both inhibiting enzyme activity directly and promoting dephosphorylation. Acetylation of GP Lys470 enhances its interaction with the PP1 substrate targeting subunit, GL, and PP1, thereby promoting GP dephosphorylation and inactivation. We show that GP acetylation is stimulated by glucose and insulin and inhibited by glucagon. Our results provide molecular insights into the intricate regulation of the classical GP and a functional cross-talk between protein acetylation and phosphorylation.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
4.8
作者：
Brady, MJ;Printen, JA;Saltiel, AR
通讯作者：
Saltiel, AR
影响因子：
13.8
作者：
Guan, Kun-Liang;Xiong, Yue
通讯作者：
Xiong, Yue
DOI：
10.1073/pnas.51.5.786
发表时间：
1964-01-01
影响因子：
11.1
作者：
ALLFREY, VG;FAULKNER, R;MIRSKY, AE
通讯作者：
MIRSKY, AE
影响因子：
2.9
作者：
Buchbinder, JL;Luong, CBH;Fletterick, RJ
通讯作者：
Fletterick, RJ