I. Hers, J. Tavaré, R. Denton
Nov 5, 1999
Citations
5
Influential Citations
136
Citations
Quality indicators
Journal
FEBS Letters
Abstract
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.