The protein kinase C inhibitors bisindolylmaleimide I (GF 109203x) and IX (Ro 31‐8220) are potent inhibitors of glycogen synthase kinase‐3 activity

FEBS Letters

Denton, Richard M¹  Tavaré, Jeremy M¹  Hers, Ingeborg¹ 

[1] Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK

关键词: Insulin;    Bisindolylmaleimide;    Protein kinase C inhibitor;    Glycogen synthase kinase-3;    Adipocyte;    GSK-3;    glycogen synthase kinase-3;    PKC;    protein kinase C;    JNK;    Jun-N-terminal kinase;    MAPKAP;    mitogen-activated protein kinase-activated protein;    AP-1;    activator protein-1;   

DOI  :  10.1016/S0014-5793(99)01389-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Here we report that the widely used protein kinase C inhibitors, bisindolylmaleimide I and IX, are potent inhibitors of glycogen synthase kinase-3 (GSK-3). Bisindolylmaleimide I and IX inhibited GSK-3 in vitro, when assayed either in cell lysates (IC₅₀ 360 nM and 6.8 nM, respectively) or in GSK-3β immunoprecipitates (IC₅₀ 170 nM and 2.8 nM, respectively) derived from rat epididymal adipocytes. Pretreatment of adipocytes with bisindolylmaleimide I (5 μM) and IX (2 μM) reduced GSK-3 activity in total cell lysates, to 25.1±4.3% and 12.9±3.0% of control, respectively. By contrast, bisindolylmaleimide V (5 μM), which lacks the functional groups present on bisindolylmaleimide I and IX, had little apparent effect. We propose that bisindolylmaleimide I and IX can directly inhibit GSK-3, and that this may explain some of the previously reported insulin-like effects on glycogen synthase activity.

【 授权许可】

Unknown