scholarly journals Minimum requirements for inhibition of smooth-muscle myosin light-chain kinase by synthetic peptides

1989 ◽  
Vol 257 (1) ◽  
pp. 73-78 ◽  
Author(s):  
J T Hunt ◽  
D M Floyd ◽  
V G Lee ◽  
D K Little ◽  
S Moreland
Keyword(s):  
Amino Acid ◽  
Light Chain ◽  
Synthetic Peptides ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor ◽  
Basic Amino Acid ◽  
Amino Acid Residues ◽  
Serine Residue ◽  
Minimum Requirements

Although the amino acid residues that are important for peptide substrates of myosin light-chain kinase have been reported, those that are important for peptide inhibitors of this enzyme have not previously been investigated. Synthetic peptides based on the sequence Lys11-Lys12-Arg13-Ala-Ala-Arg16-Ala-Thr-Ser19 -Asn-Val21-Phe22-Ala of the chicken gizzard myosin light chain were tested as inhibitors of pig carotid-artery myosin light-chain kinase. The basic amino acid residues of the known myosin light-chain kinase inhibitor Lys-Lys-Arg-Ala-Ala-Arg-Ala-Thr-Ser-NH2 (IC50 = 14 microM) [Pearson, Misconi & Kemp (1986) J. Biol. Chem. 261, 25-27] were shown to be the important residues that contribute to inhibitor potency, as evidence by the finding that the hexapeptide Lys-Lys-Arg-Ala-Ala-Arg-NH2 had an IC50 value of 22 microM. This indicates that binding of the phosphorylatable serine residue to myosin light-chain kinase, which is of obvious importance for a substrate, does not enhance the potency of an inhibitor. With the aim of preparing more potent inhibitors, peptides Lys-Lys-Arg-Ala-Ala-Arg-Ala-Ala-Xaa-NH2 were prepared with a variety of amino acids substituted for the phosphorylatable serine residue. None of these peptides was a more potent inhibitor than the serine peptide.

Is phosphorylation the main physiological action of myosin light chain kinase?

1994 ◽  
Vol 72 (11) ◽  
pp. 1377-1379 ◽  
Author(s):  
Setsuro Ebashi ◽  
Hideto Kuwayama
Keyword(s):  
Amino Acid ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Actin Binding ◽  
In Vitro System ◽  
Beryllium Sulfate ◽  
Kinase Phosphorylation ◽  
Actin Binding Site

The 155-kDa component of bovine stomach, which exhibits a strong actomyosin (AM) activating activity and a relatively weak myosin light chain kinase (MLCK) activity, has a strong affinity for the actin filament and the actin-binding site is confined to an 80 amino acid residue on its N-terminal side. This affinity may play a crucial role in AM activation. Some reagents preferentially abolish either the AM-activating effect or MLCK activity. In conclusion, MLCK of the 155-kDa component does not play a fundamental role in activating the AM system as far as the in vitro system is concerned. The possible mechanism of AM activation by the component is discussed.Key words: myosin light chain kinase, phosphorylation of myosin light chain, leiotonin, wortmannin, beryllium sulfate.

scholarly journals Zinc exocytosis is sensitive to myosin light chain kinase inhibition in mouse and human eggs

2020 ◽  
Vol 26 (4) ◽  
pp. 228-239 ◽  
Author(s):  
Hoi Chang Lee ◽  
Maxwell E Edmonds ◽  
Francesca E Duncan ◽  
Thomas V O’Halloran ◽  
Teresa K Woodruff
Keyword(s):  
Embryo Development ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor ◽  
Early Embryo ◽  
Egg Activation ◽  
Cortical Granules ◽  
Preimplantation Embryo Development ◽  
Egg Maturation

Abstract Zinc dynamics are essential for oocyte meiotic maturation, egg activation, and preimplantation embryo development. During fertilisation and egg activation, the egg releases billions of zinc atoms (Zn2+) in an exocytotic event termed the ‘zinc spark’. We hypothesised that this zinc transport and exocytosis is dependent upon the intracellular trafficking of cortical granules (CG) which requires myosin-actin-dependent motors. Treatment of mature mouse and human eggs with ML-7, a myosin light chain kinase inhibitor (MLCK), resulted in an 80% reduction in zinc spark intensity compared to untreated controls when activated with ionomycin. Moreover, CG migration towards the plasma membrane was significantly decreased in ML-7-treated eggs compared with controls when activated parthenogenetically with ionomycin. In sperm-induced fertilisation via intracytoplasmic sperm injection (ICSI), ML-7-treated mouse eggs exhibited decreased labile zinc intensity and cortical CG staining. Collectively, these data demonstrate that ML-7 treatment impairs zinc release from both murine and human eggs after activation, demonstrating that zinc exocytosis requires myosin light chain kinase activity. Further, these results provide additional support that zinc is likely stored and released from CGs. These data underscore the importance of intracellular zinc trafficking as a crucial component of egg maturation necessary for egg activation and early embryo development.

Amino acid sequence of rabbit ventricular myosin light chain-2: Identity with the slow skeletal muscle isoform

1986 ◽  
Vol 6 (7) ◽  
pp. 655-661 ◽  
Author(s):  
John H. Collins ◽  
Janet L. Theibert ◽  
Luciano Dalla Libera
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Strong Support ◽  
Sequence Information ◽  
Myosin Isoforms ◽  
Amino Acid Residues ◽  
Myosin Light Chain 2 ◽  
Muscle Types

Many studies have established a correlation of differences in the activities of various muscle types with differences in the expression of myosin isoforms. In this paper we report the sequence determination of myosin light chain-2 from rabbit slow skeletal (LC2s) and ventricular (LC2v) nmscles. We sequenced tryptic peptides from LC2v which account for all except a few terminal amino acid residues. The major part (87 residues) of the rabbit LC2s sequence, obtained from tryptic and cyanogen bromide (CNBr) peptides, was found to be identical to rabbit LC2v. Our results provide the first sequence information on LC2s from any species, and lend strong support to the hypothesis that LC2s and LC2v are identical. Comparisons of rabbit LC2v and LC2s with rabbit LC2f (from fast skeletal muscle), and also with chicken LC2f and LC2v, show clearly that LC2s and LC2v from mammalian and avian species are more closely related to each other than they are to LC2f isoforms from the same species.

Myosin Light Chain Kinase Inhibitor Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice

2012 ◽  
Vol 58 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Xiaochang Liu ◽  
Jianming Xu ◽  
Qiao Mei ◽  
Liang Han ◽  
Jian Huang
Keyword(s):  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Kinase Inhibitor

scholarly journals Total Synthesis of MS-444, a Myosin Light Chain Kinase Inhibitor

1997 ◽  
Vol 50 (3) ◽  
pp. 289-290 ◽  
Author(s):  
KUNIAKI TATSUTA ◽  
TAKUJI YOSHIMOTO ◽  
HIROKI GUNJI
Keyword(s):  
Total Synthesis ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor

scholarly journals Participation of protein kinases in complement C5b-9-induced shedding of platelet plasma membrane vesicles

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2880-2886
Author(s):  
T Wiedmer ◽  
PJ Sims
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor ◽  
Complement Proteins ◽  
Cellular Events ◽  
Microparticle Formation ◽  
Terminal Complement

The formation of membrane microparticles through vesiculation of the platelet plasma membrane is known to provide catalytic surface for several enzyme complexes of the coagulation system, and to underlie the procoagulant responses elicited with platelet activation. This induced shedding of vesicles from the plasma membrane is most prominent when platelets are activated by the terminal complement proteins, C5b-9, by a Ca2+ ionophore, or by the combination of thrombin plus collagen. Although shown to require elevated [Ca2+], the cellular events that initiate plasma membrane evagination and fusion to form the shed vesicles remain unresolved. To gain additional insight into the cellular events that regulate membrane microparticle formation, we have examined how this process is influenced by the activity of cellular protein kinases. Cytoplasmic [Ca2+] of gel-filtered platelets was increased by membrane assembly of the terminal complement proteins C5b- 9 in the presence of selective inhibitors of protein kinase or phosphatase reactions, and resulting microparticle formation was quantitated by fluorescence-gated flow cytometry. Pre-equilibration of the phosphatase inhibitor vanadate into the platelet cytosol increased microparticle formation by as much as 40%, suggesting that vesiculation of the platelet plasma membrane is influenced by the state of phosphorylation of a cellular constituent. By contrast to the stimulatory effects of vanadate, microparticle formation was partially inhibited in platelets treated with the protein kinase inhibitor sphingosine, the myosin light chain kinase inhibitor ML-7, the calmodulin-antagonist W-7, and under conditions of elevated cytosolic concentration of cyclic adenosine monophosphate. These results indicate that complement-induced platelet microparticle formation is influenced by one or more protein kinase(s) as well as by calmodulin, and suggest a role for the platelet myosin light chain kinase or another Ca(2+)- pluscalmodulin-regulated membrane component.

52 A NOVEL MYOSIN LIGHT CHAIN KINASE INHIBITOR, PIK, PROTECTS FROM LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY.

2007 ◽  
Vol 55 (2) ◽  
pp. S357.1-S357
Author(s):  
T. Mirzapoiazova ◽  
S. Sammani ◽  
L. Moreno ◽  
S. M. Dudek ◽  
J. R. Turner ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor
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