A novel highly specific and potent inhibitor of calmodulin-dependent protein kinase II.
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.
Ishida
A
A
Department of Biochemistry, Asahikawa Medical College, Japan.
Kameshita
I
I
Okuno
S
S
Kitani
T
T
Fujisawa
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001667:Binding, Competitive; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D002417:Cattle; D002540:Cerebral Cortex / Q000201:enzymology; D002645:Chickens; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010455:Peptides; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C085903:autocamtide-2; C072105:KN 93; D000096926:Benzenesulfonamides