Unknown

Dataset Information

0

Modulation of GSK3? autoinhibition by Thr-7 and Thr-8.


ABSTRACT: Glycogen synthase kinase 3? (GSK-3?) 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? by AKT is an important mechanism for negative regulation of GSK3? activity upon insulin stimulation. Here, we report that Thr-7 and Thr-8 residues located in the AKT/PKB substrate consensus sequence on GSK3? are essential for insulin-stimulated Ser-9 phosphorylation in vivo and for GSK3? inactivation. Intestinal cell kinase (ICK) phosphorylates GSK3? Thr-7 in vitro and in vivo. Thr-8 phosphorylation partially inhibits GSK3?, but Thr-7 phosphorylation promotes GSK3? activity and blocks phospho-Ser-9-dependent GSK3? autoinhibition. Our findings uncover novel mechanistic and signaling inputs involved in the autoinhibition of GSK3?.

SUBMITTER: Tong Y 

PROVIDER: S-EPMC5829016 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Modulation of GSK3β autoinhibition by Thr-7 and Thr-8.

Tong Yixin Y   Park Sohyun S   Wu Di D   Harris Thurl E TE   Moskaluk Christopher A CA   Brautigan David L DL   Fu Zheng Z  

FEBS letters 20180208 4


Glycogen synthase kinase 3β (GSK-3β) 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 GSK3β by AKT is an important mechanism for negative regulation of GSK3β activity upon insulin stimulation. Here, we report that Thr-7 and Thr-8 residues located in the AKT/PKB substrate consensus sequence on GSK3β are essential for insulin-stimulated Ser-9  ...[more]

Similar Datasets

| S-EPMC3467206 | biostudies-literature
| S-EPMC7368652 | biostudies-literature
| S-EPMC4207903 | biostudies-literature
| S-EPMC3047067 | biostudies-literature
| S-EPMC7900441 | biostudies-literature
| S-EPMC2636752 | biostudies-literature
| S-EPMC7149226 | biostudies-literature
| PRJNA209994 | ENA
| S-EPMC4514647 | biostudies-literature
| S-EPMC5472658 | biostudies-literature