Abstract

The general objective of this proposal is to elucidate the mechanisms by which the interaction of actin and myosin underlying contraction is regulated in vascular smooth muscle. This proposal is intended to study the role of myosin light chain phosphorylation, Ca2+ binding to myosin, and leiotonins on the regulation of actin-activated ATPase activity of myosin isolated from arterial and visceral smooth muscles. The exitence of a dual CA2+ regulation, one mediated my myosin and the other mediated by CA2+ binding regulatory proteins (e.g. leiotonins) located in the thin filament, will be investigated. The role of 20,000 dalton light chain on the regulation of actomyosin ATPase will be studied using myosin deficient in light chain and by exchanging light chain between myosin that does not exhibit direct myosin mediated calcium sensitivity after phosphorylection (e.g. gizzard myosin, stomach muscle myosin) and myosin that does exhibit calcium sensitivitiy (e.g vas deferens myosin, arterial myosin). Furthermore; the role of tropomyosin on the regulation of actin-activated myosin ATPase activity will be determined using HMM and S-1 prepared from smooth muscle.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL022264-07
Application #
3336809
Study Section
Physiology Study Section (PHY)
Project Start
1978-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1987-03-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Horiuchi, K Y; Chacko, S (1991) The mechanism for the inhibition of actin-activated ATPase of smooth muscle heavy meromyosin by calponin. Biochem Biophys Res Commun 176:1487-93
Horiuchi, K Y; Samuel, M; Chacko, S (1991) Mechanism for the inhibition of acto-heavy meromyosin ATPase by the actin/calmodulin binding domain of caldesmon. Biochemistry 30:712-7
Chacko, S; Eisenberg, E (1990) Cooperativity of actin-activated ATPase of gizzard heavy meromyosin in the presence of gizzard tropomyosin. J Biol Chem 265:2105-10
Horiuchi, K Y; Chacko, S (1989) Caldesmon inhibits the cooperative turning-on of the smooth muscle heavy meromyosin by tropomyosin-actin. Biochemistry 28:9111-6
Katayama, E; Horiuchi, K Y; Chacko, S (1989) Characteristics of the myosin and tropomyosin binding regions of the smooth muscle caldesmon. Biochem Biophys Res Commun 160:1316-22
Horiuchi, K Y; Chacko, S (1988) Interaction between caldesmon and tropomyosin in the presence and absence of smooth muscle actin. Biochemistry 27:8388-93
Fillers, W S; Chacko, S (1987) Modulation of monomer-polymer equilibrium of phosphorylated smooth muscle myosin: effects on actin activation. Biochemistry 26:5896-903
Chacko, S; Miyata, H; Horiuchi, K Y (1987) Modulation of actomyosin ATPase by thin filament-associated proteins. Prog Clin Biol Res 245:143-58
Miyata, H; Chacko, S (1986) Role of tropomyosin in smooth muscle contraction: effect of tropomyosin binding to actin on actin activation of myosin ATPase. Biochemistry 25:2725-9
Horiuchi, K Y; Miyata, H; Chacko, S (1986) Modulation of smooth muscle actomyosin ATPase by thin filament associated proteins. Biochem Biophys Res Commun 136:962-8

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