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Regulation of Myosin Light Chain Kinase Activity in Smooth Muscle

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Regulation of the Contractile Cycle in Smooth Muscle

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Summary

Phosphorylation of myosin regulatory light chain by Ca2+/calmodulindependent myosin light chain kinase (MLCK) plays a central role in smooth muscle contractility. The quantitative relation between intracellular Ca2+ concentrations and light chain phosphorylation is not fixed but modulated dynamically by various regulatory processes. Most of the calmodulin in smooth muscle cells is tightly bound to cellular elements even in the absence of Ca2+. Surprisingly, even the most mobile fraction (8% of the total) has a diffusion coefficient in smooth muscle cells sevenfold lower than a freely diffusible, similar size dextran. The possibility is considered that calmodulin available for MLCK activation is limiting. Furthermore, calmodulin availability may be regulated by unidentified processes. The multifunctional Ca2+/ calmodulin-dependent protein kinase II phosphorylates MLCK adjacent to the C-terminus of the calmodulin-binding domain. This phosphorylation increases the concentration of Ca2+/calmodulin required for activation and hence physiologically increases the Ca z concentration required for light chain phosphorylation. However, in smooth muscle cells the concentration of Ca2+ necessary for MLCK phosphorylation is greater than that required for light chain phosphorylation. Thus MLCK is sensitive to small increases in Ca2+ during the initiation of contraction and subsequently becomes desensitized to Ca2+ after phosphorylation, thereby limiting light chain phosphorylation.

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Authors and Affiliations

  1. Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX, 75235-9040, USA

    Kristine E. Kamm, Katherine Luby-Phelps, Malu G. Tansey, Patricia J. Gallagher & James T. Stull

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  1. Kristine E. Kamm
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  2. Katherine Luby-Phelps
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  3. Malu G. Tansey
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  4. Patricia J. Gallagher
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  5. James T. Stull
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Editors and Affiliations

  1. Mie University of School Medicine, 2-175 Edobashi, Tsu, Mie, 514, Japan

    Takeshi Nakano M.D., Ph.D. (Professor) (Professor)

  2. University of Arizona, 85721, Tucson, AZ, USA

    David J. Hartshorne Ph.D. (Professor) (Professor)

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© 1995 Springer-Verlag Tokyo

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Kamm, K.E., Luby-Phelps, K., Tansey, M.G., Gallagher, P.J., Stull, J.T. (1995). Regulation of Myosin Light Chain Kinase Activity in Smooth Muscle. In: Nakano, T., Hartshorne, D.J. (eds) Regulation of the Contractile Cycle in Smooth Muscle. Springer, Tokyo. https://doi.org/10.1007/978-4-431-65880-1_9

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  • DOI: https://doi.org/10.1007/978-4-431-65880-1_9

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-65882-5

  • Online ISBN: 978-4-431-65880-1

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