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The protein kinase C inhibitors bisindolylmaleimide I (GF 109203x) and IX (Ro 31‐8220) are potent inhibitors of glycogen synthase kinase‐3 activity
Author(s) -
Hers Ingeborg,
Tavaré Jeremy M,
Denton Richard M
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01389-7
Subject(s) - bisindolylmaleimide , gsk 3 , protein kinase c , glycogen synthase , protein kinase a , chemistry , kinase , endocrinology , phosphorylation , medicine , biochemistry , biology
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 (IC 50 360 nM and 6.8 nM, respectively) or in GSK‐3β immunoprecipitates (IC 50 170 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.