Tyrosine dephosphorylation of glycogen synthase kinase‐3 is involved in its extracellular signal‐dependent inactivation

FEBS Letters

Murai, Hiroshi¹  Okazaki, Michiko¹  Kikuchi, Akira¹ 

[1] Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan

关键词: GSK-3;    Insulin;    Tyrosine dephosphorylation;    Protein kinase C;    GSK-3;    glycogen synthase kinase-3;    EGF;    epidermal growth factor;    TPA;    12-O-tetradecanoylphorbol 13-acetate;    CHO-IR cells;    Chinese hamster ovary cells overexpressing the human insulin receptor;    p90rsk;    90 kDa ribosomal protein S6 kinase;    MAPKAP;    mitogen-activated protein kinase-activated protein;    MAPK;    mitogen-activated protein kinase;    PKB;    protein kinase B;    PI;    phosphatidylinositol;    PP2A;    protein phosphatase 2A;    HA;    hemaggulutinin;    PDBu;    phorbol 12;    13-dibutyrate;   

DOI  :  10.1016/0014-5793(96)00806-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown