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

[No Value] Hers, JM Tavare, RM Denton

Research output: Contribution to journalArticle (Academic Journal)peer-review

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-3 beta immunoprecipitates (IC50 170 nM and 2.8 nM, respectively) derived from rat epididymal adipocytes. Pretreatment of adipocytes with bisindolylmaleimide I (5 mu M) and IX (2 mu M) 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 mu M), 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. (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)433-436
Number of pages4
JournalFEBS Letters
Volume460
Issue number3
Publication statusPublished - 5 Nov 1999

Keywords

  • insulin
  • bisindolylmaleimide
  • protein kinase C inhibitor
  • glycogen synthase kinase-3
  • adipocyte
  • EPIDIDYMAL FAT-CELLS
  • SELECTIVE INHIBITORS
  • INSULIN
  • PHOSPHORYLATION
  • JUN
  • PHOSPHATASE-1
  • ACTIVATION
  • EXTRACTS

Cite this