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G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle.
Open accessAbstract
The mechanism of G protein-mediated sensitization of the contractile apparatus of smooth muscle to Ca2+ was studied in receptor-coupled alpha-toxin-permeabilized rabbit portal vein smooth muscle. To test the hypothesis that Ca2+ sensitization is due to inhibition of myosin light-chain (MLC) phosphatase activity, we measured the effect of guanosine 5'-[gamma-thio]triphosphate and phenylephrine on the rate of MLC dephosphorylation in muscles preactivated with Ca2+ and incubated in Ca(2+)- and ATP-free solution containing 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9) to block MLC kinase activity. Guanosine 5'-[gamma-thio]triphosphate alone (300 microM) or in combination (3 microM) with phenylephrine decreased the rates of relaxation and dephosphorylation of MLC to about half of control values; this inhibition is sufficient to account for maximal G protein-mediated Ca2+ sensitization of MLC phosphorylation. The rate of thiophosphorylation of MLC with adenosine 5'-[gamma-thio]-triphosphate was not affected by guanosine 5'-[gamma-thio]triphosphate. We suggest that inhibition of protein phosphatase(s) by G protein(s) may have important regulatory functions.
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Citations
Cited by
Signal transduction and regulation in smooth muscle
Somlyo, A. P., & Somlyo, A. V. (1994) · Nature · doi:10.1038/372231a0 · Cited by 1,902
Self-citationSomlyo, A. P., & Somlyo, A. V. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-2-00177.x · Cited by 1,207
Self-citationRegulation of the Cytoskeleton and Cell Adhesion by the Rho Family GTPases in Mammalian Cells
Kaibuchi, K., Kuroda, S., & Amano, M. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.459 · Cited by 1,017
Calcium Movements, Distribution, and Functions in Smooth Muscle
Karaki, H., Ozaki, H., Hori, M., Mitsui-Saito, M., Amano, K.-I., Harada, K.-I., Miyamoto, S., Nakazawa, H., Won, K.-J., & Sato, K. (1997) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01321-8 · Cited by 743
Myosin light chain phosphatase: subunit composition, interactions and regulation
Hartshorne, D. J., Ito, M., & Erdo¨di, F. (1998) · Journal of Muscle Research & Cell Motility · doi:10.1023/a:1005385302064 · Cited by 403
Metadata
- Authors
- Kitazawa, T., Masuo, M., & Somlyo, A. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1991-10-15
- Volume
- 88
- Issue
- 20
- Pages
- 9307-9310
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2014234136
- Cited by
- 320
- References
- 0
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- green
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- Kitazawa, T., Masuo, M., & Somlyo, A. P. (1991). G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.88.20.9307
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