title: ATP competitive protein kinase C inhibitors demonstrate distinct state-dependent inhibition.
abstract: We previously reported that some ATP competitive protein kinase C (PKC) inhibitors are either competitive or uncompetitive inhibitors with respect to substrate peptides. In this report, we demonstrate how the interactions between PKC and inhibitors change PKC activation kinetics. A substrate competitive inhibitor, bisindolylmaleimide I, targets activated PKC and stabilizes PKC in the activated conformation. This leads to transient activation and prolonged deactivation of PKC in the presence of bisindolylmaleimide I. In contrast, an uncompetitive substrate inhibitor, bisindolylmaleimide IV, targets quiescent PKC and stabilizes PKC in the quiescent conformation, which generates slower activation and suppressed translocation upon activation of PKC.
authors: Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.
authors: Ida M
authors: IM
authors: Smith
authors: Naoto
authors: N
authors: Hoshi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D006801:Humans; D007211:Indoles; D007700:Kinetics; D008301:Maleimides; D011487:Protein Conformation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D055550:Protein Stability
chemical_list: D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; C070515:bisindolylmaleimide I