title: Peptide analogs of the pseudosubstrate domain of smooth muscle myosin light chain kinase inhibit actomyosin ATPase activity at concentrations that do not inhibit superprecipitation.
abstract: The inhibitory effect of calmodulin antagonists, synthetic peptide analogs of the pseudosubstrate domain of smooth muscle MLC kinase, and an inhibitor based on the sequence of MLC were examined using bovine aortic actomyosin and isolated chicken gizzard MLC. Much lower concentrations of the peptides were necessary to inhibit actomyosin ATPase activity than to inhibit superprecipitation. In contrast, calmodulin antagonists inhibited both ATPase activity and superprecipitation at similar concentrations. The peptide analogs were competitive with isolated MLC, but not calmodulin, for inhibition of MLC kinase. These results suggest that in addition to the calmodulin dependence of MLC phosphorylation, a second calmodulin-like protein may be important in actin-myosin interactions. The data also suggest that the pseudosubstrate hypothesis may not completely account for regulation of MLC kinase activity.
authors.affiliation: Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543.
authors.forename: S
authors.initials: S
authors.lastname: Moreland
authors.forename: M
authors.initials: M
authors.lastname: Ikebe
authors.forename: J T
authors.initials: JT
authors.lastname: Hunt
authors.forename: R S
authors.initials: RS
authors.lastname: Moreland
mesh_terms: D000205:Actomyosin / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002417:Cattle; D011232:Chemical Precipitation; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009218:Myosins / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000494:pharmacology
chemical_list: D002147:Calmodulin; D009842:Oligopeptides; C076926:SQ 31429; C076927:lysyl-arginyl-arginyltryptophyl-lysyl-lysine; C076928:lysyl-arginyl-arginyl-phenylalanyl-lysyl-lysine; C076929:SQ 32732; D000205:Actomyosin; D009219:Myosin-Light-Chain Kinase; D009218:Myosins