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Tyrosine dephosphorylation of glycogen synthase kinase‐3 is involved in its extracellular signal‐dependent inactivation
Author(s) -
Murai Hiroshi,
Okazaki Michiko,
Kikuchi Akira
Publication year - 1996
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 - 10.1016/0014-5793(96)00806-x
Subject(s) - dephosphorylation , extracellular , gsk 3 , phosphorylation , glycogen synthase , chemistry , biochemistry , glycogen phosphorylase , microbiology and biotechnology , kinase , gsk3b , phosphorylase kinase , glycogen , biology , phosphatase
We examined whether extracellular signals regulate glycogen synthase kinase‐3 (GSK‐3) activity through tyrosine dephosphorylation of GSK‐3. In resting Chinese hamster ovary cells overexpressing the human insulin receptor (CHO‐IR cells), GSK‐3 was tyrosine‐phosphorylated and active. Insulin and 12‐ O ‐tetradecanoylphorbol 13‐acetate (TPA) induced inactivation and tyrosine dephosphorylation of GSK‐3. It is known that Ser‐9 of GSK‐3β is phosphorylated in response to insulin and that the phosphorylation of this amino acid residue causes inactivation of GSK‐3β. However, the ectopically expressed GSK‐3β Δ9 , in which the N‐terminal nine amino acids of GSK‐3β were deleted, was still inactivated and tyrosine‐dephosphorylated in response to insulin. Protein phosphatase 2A treatment partially reversed insulin‐induced GSK‐3β inactivation, but did not change GSK‐β Δ9 inactivation. In CHO‐IR cells where protein kinase C was down‐regulated, TPA neither inactivated nor tyrosine‐dephosphorylated GSK‐3. However, insulin inactivated and tyrosine‐dephosphorylated GSK‐3, although to a lesser degree than in the control cells. These results suggest that in addition to serine phosphorylation, tyrosine dephosphorylation of GSK‐3 is also important for the regulation of GSK‐3 activity in response to extracellular signals and that insulin regulates GSK‐3 activity through both protein kinase C‐dependent as well as protein kinase C‐independent pathways.