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