Glycogen synthase kinase 3 beta (GSK-3 beta) is a pivotal signaling node that regulates a myriad of cellular functions and is deregulated in many pathological conditions, making it an attractive therapeutic target. Inhibitory Ser-9 phosphorylation of GSK3 beta by AKT is an important mechanism for negative regulation of GSK3 beta activity upon insulin stimulation. Here, we report that Thr-7 and Thr-8 residues located in the AKT/PKB substrate consensus sequence on GSK3 beta are essential for insulin-stimulated Ser-9 phosphorylation in vivo and for GSK3 beta inactivation. Intestinal cell kinase (ICK) phosphorylates GSK3 beta Thr-7 in vitro and in vivo. Thr-8 phosphorylation partially inhibits GSK3 beta, but Thr-7 phosphorylation promotes GSK3 beta activity and blocks phospho-Ser-9-dependent GSK3 beta autoinhibition. Our findings uncover novel mechanistic and signaling inputs involved in the autoinhibition of GSK3 beta.
第一作者单位：[1]Univ Virginia, Dept Pharmacol, POB 800735,1340 Jefferson Pk Ave, Charlottesville, VA 22908 USA[2]Huazhong Univ Sci & Technol,Tongji Hosp,Gastrointestinal Surg Ctr,Wuhan,Hubei,Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Tong Yixin,Park Sohyun,Wu Di,et al.Modulation of GSK3β autoinhibition by Thr-7 and Thr-8[J].FEBS LETTERS.2018,592(4):537-546.doi:10.1002/1873-3468.12990.
APA：
Tong, Yixin,Park, Sohyun,Wu, Di,Harris, Thurl E.,Moskaluk, Christopher A....&Fu, Zheng.(2018).Modulation of GSK3β autoinhibition by Thr-7 and Thr-8.FEBS LETTERS,592,(4)
MLA：
Tong, Yixin,et al."Modulation of GSK3β autoinhibition by Thr-7 and Thr-8".FEBS LETTERS 592..4(2018):537-546
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