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

Yixin Tong, Sohyun Park, Di Wu, Thurl E. Harris, Christopher A. Moskaluk, David L. Brautigan, Zheng Fu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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 phosphorylation in vivo and for GSK3β inactivation. Intestinal cell kinase (ICK) phosphorylates GSK3β Thr-7 in vitro and in vivo. Thr-8 phosphorylation partially inhibits GSK3β, but Thr-7 phosphorylation promotes GSK3β activity and blocks phospho-Ser-9-dependent GSK3β autoinhibition. Our findings uncover novel mechanistic and signaling inputs involved in the autoinhibition of GSK3β.

Original languageEnglish
Pages (from-to)537-546
Number of pages10
JournalFEBS Letters
Issue number4
StatePublished - Feb 2018
Externally publishedYes


  • AKT
  • GSK3β
  • ICK
  • autoinhibition
  • insulin
  • phosphorylation


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