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Modulation of GSK 3β autoinhibition by Thr‐7 and Thr‐8
Author(s) -
Tong Yixin,
Park Sohyun,
Wu Di,
Harris Thurl E.,
Moskaluk Christopher A.,
Brautigan David L.,
Fu Zheng
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12990
Subject(s) - phosphorylation , gsk 3 , protein kinase b , chemistry , microbiology and biotechnology , glycogen synthase , gsk3b , signal transduction , biochemistry , in vivo , kinase , biology
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 GSK 3β by AKT is an important mechanism for negative regulation of GSK 3β activity upon insulin stimulation. Here, we report that Thr‐7 and Thr‐8 residues located in the AKT / PKB substrate consensus sequence on GSK 3β are essential for insulin‐stimulated Ser‐9 phosphorylation in vivo and for GSK 3β inactivation. Intestinal cell kinase ( ICK ) phosphorylates GSK 3β Thr‐7 in vitro and in vivo . Thr‐8 phosphorylation partially inhibits GSK 3β, but Thr‐7 phosphorylation promotes GSK 3β activity and blocks phospho‐Ser‐9‐dependent GSK 3β autoinhibition. Our findings uncover novel mechanistic and signaling inputs involved in the autoinhibition of GSK 3β.