Inhibition of calmodulin-dependent myosin light-chain kinase by growth-hormone-releasing factor and vasoactive intestinal peptide.
In view of the ability of calmodulin to bind vasoactive intestinal peptide (VIP) and growth-hormone-releasing factor (GRF) with high affinity [Stallwood, Brugger, Baggenstoss, Stemmer, Shiraga, Landers and Paul (1992) J. Biol. Chem. 267, 19617-19621], the effects of these neuropeptides on a model calmodulin-dependent enzyme, myosin light-chain kinase (MLCK), were studied. Both peptides were potent inhibitors of MLCK activity. The inhibition of enzyme activity by VIP and GRF was progressively overcome with increasing calmodulin concentrations, with no inhibition observed at a saturating calmodulin concentration. Nanomolar concentrations of MLCK blocked the formation of calmodulin-[125I-Tyr10]VIP complexes. These data provide support for a functional role of VIP and GRF binding by calmodulin.
Shiraga
H
H
Department of Anesthesiology, University of Nebraska Medical Center, Omaha 68198-6830.
Stallwood
D
D
Ebadi
M
M
Pfeiffer
R
R
Landers
D
D
Paul
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002147:Calmodulin; D009842:Oligopeptides; D014660:Vasoactive Intestinal Peptide; C087887:kemptamide; D013007:Growth Hormone-Releasing Hormone; D009219:Myosin-Light-Chain Kinase