A novel highly specific and potent inhibitor of calmodulin-dependent protein kinase II

Biochem Biophys Res Commun. 1995 Jul 26;212(3):806-12. doi: 10.1006/bbrc.1995.2040.

Abstract

A novel synthetic peptide AIP (autocamtide-2-related inhibitory peptide), a nonphosphorylatable analog of autocamtide-2, was found to be a highly specific and potent inhibitor of calmodulin-dependent protein kinase II (CaM-kinase II). It was 50 and 500 times more potent than CaMK-(281-302Ala286) and KN-93, respectively, under the assay conditions used. The inhibition was unaffected by the presence or absence of Ca2+/calmodulin, and it was competitive with autocamtide-2 and noncompetitive with syntide-2. AIP (1 microM) completely inhibited CaM-kinase II activity, but did not affect cyclic AMP-dependent protein kinase, protein kinase C, calmodulin-dependent protein kinase IV, and unidentified protein kinases occurring in a rat brain extract. These results indicate that AIP is a useful tool for studying the physiological roles of CaM-kinase II.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Benzylamines / pharmacology
  • Binding, Competitive
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Cattle
  • Cerebral Cortex / enzymology
  • Chickens
  • In Vitro Techniques
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protein Kinase Inhibitors
  • Rats
  • Sulfonamides / pharmacology

Substances

  • Benzylamines
  • Peptides
  • Protein Kinase Inhibitors
  • Sulfonamides
  • autocamtide-2
  • KN 93
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases