Skip to main content
SpringerLink
Log in
Book cover

Molecular and Cellular Aspects of Muscle Contraction pp 67–75Cite as

Regulation of the RHO Signaling Pathway by Excitatory Agonists in Vascular Smooth Muscle

  • Conference paper

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 538))

Abstract

It has been established in smooth muscle that binding of excitatory agonists to specific cell surface receptors, most of which belong to a heptahelical type of G protein-coupled receptors, leads to the activation of phospholipase C and the opening of Ca2+ channels on the plasma membrane.1′2 Phospholipase C activation generates the two second messengers, inositol-1, 4, 5-trisphosphate and 1, l-diacylglycerol. Inositol-1, 4, 5-trisphosphate stimulates Ca2+ release from an intracellular Ca2+ store, which, together with stimulated Ca2+ influx across the plasma membrane, brings about an increase in the intracellular free Ca2+ concentration ([Ca2+]i). An increase in the [Ca2+]i activates the Ca2+, calmodulin-dependent enzyme myosin light chain kinase (MLCK), which phosphorylates the 20 kDa myosin light chain (MLC), leading to the initiation of a contractile response.3 An increase in the membrane content of 1, 2-diacy lglycerol leads to activation of protein kinase C, which activates a contractile mechanism independently of or synergistically with an increase in the [Ca2+]i.1,2

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. H. Rasmussen, Y. Takuwa, and S. Park, Protein kinase C in the regulation of smooth muscle contraction, FASEBJ. 1, 177–185 (1995)

    Google Scholar 

  2. Y. Takuwa, Regulation of vascular smooth muscle contraction. The roles of Ca2+, protein kinase C and myosin light chain phosphatase, Jpn. Heart J. 37, 793–813 (1996)

    Article  PubMed  CAS  Google Scholar 

  3. K. E. Kamm, and J. T. Stull, The function of myosin and myosin light chain kinase phosphorylation in smooth muscle, Annu. Rev. Pharmacol Toxicol, 25, 593–620 (1985)

    Article  PubMed  CAS  Google Scholar 

  4. P. Somlyo, and A. V. Somlyo. Signal transduction by G-proteins, Rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II, J Physiol(Lond) 522, 177–185 (2000)

    Article  CAS  Google Scholar 

  5. J. P. Morgan, and K. G. Morgan, Stimulus-specific patterns of intracellular calcium levels in smooth muscle of ferret portal vein, J. Physiol. (London), 351, 155–167 (1984)

    CAS  Google Scholar 

  6. M. Rembold, and R. A. Murphy, Myoplasmic [Ca2+]i determines myosin phosphorylation in agonist-stimulated swine arterial smooth muscle, Cir. Res. 63, 593–603 (1988)

    Article  CAS  Google Scholar 

  7. D-C. Tang, J. T. Stull, Y. Kubota, and K. E. Kamm, Regulation of the Ca2+ dependent of smooth muscle contraction, J. Biol Chem. 267, 11839–11845 (1992)

    PubMed  CAS  Google Scholar 

  8. T. Kitazawa, S. Kobayashi, K. Horiuti, A. V. Somlyo, and A. P. Somlyo, Receptor-coupled, permeabilized smooth muscle. Role of the phosphatidylinositol cascade, G proteins, and modulation of the contractile response to Ca2+, J. Biol. Chem. 264, 5339–5342 (1989)

    PubMed  CAS  Google Scholar 

  9. T. Kitazawa, B. D. Gaylinn, G. H. Denney, and A. P. Somlyo, G-protein-mediated Ca2+ sensitization of smooth muscle contraction through myosin light chain phosphorylation, J. Biol. Chem. 266, 1708–1715 (1991)

    PubMed  CAS  Google Scholar 

  10. T. Kitazawa, M. Masuo, and A. P. Somlyo, G Protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle, Proc. Natl. Acad. Sci. USA 88, 9307–9310 (1991)

    Article  PubMed  CAS  Google Scholar 

  11. Y. Kubota, M. Nomura, K. E. Kamm, M. C. Mumby, and J. T. Stull, GTPrS-dependent regulation of smooth muscle contractile elements, Am. J. Physiol. 262, C405–C410 (1992)

    PubMed  CAS  Google Scholar 

  12. H. Nagumo, Y. Sasaki, Y. Ono, H. Okamoto, M. Seto, and Y. Takuwa, Rho kinase inhibitor HA1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells. Am. J. Physiol. 278, C57–C65 (2000)

    CAS  Google Scholar 

  13. Alessi, L. K. Macdougall, M. M. Sola, M. Ikebe, and P. Cohen, The control of protein phosphatase-1 by targeting sub un its. The major myosin phosphatase in avian smooth muscle is a novel form of protein phosphatase-l. Eur. J.Biochem. 210, 1023–1035 (1992)

    Article  PubMed  CAS  Google Scholar 

  14. .H. Shimizu, M. Ito, M. Miyahara, K. Ichikawa, S. Okubo, T. Konishi, M. Naka, T. Tanaka, K. Hirano, and D. J. Hartshome, Characterization of the myosin-binding subunit of smooth muscle myosin phosphatase, J. Biol. Chem. 269, 30407–30411 (1994)

    PubMed  CAS  Google Scholar 

  15. K. Hirata, A. Kikuchi, S. Sasaki, S. Kuroda, K. Kaibuchi, Y. Matsuura, H. Seki, K. Saida, and Y. Takai, Involvement of rho p21 in the GTPvS-enhanced calcium ion sensitivity of smooth muscle contraction, J. Biol. Chem. 267, 8719–8722 (1992)

    PubMed  CAS  Google Scholar 

  16. Fujita, T. Takeuchi, H. Nakajima, H. Nishio, and F. Hata, Involvement of heterotrimeric GTP-binding protein and Rho protein, but not protein kinase C, in agonist-induced Ca2+ sensitization of skinned muscle of quinea pig vas deferens. J. Pharmacol Exp. Ther. 274, 555–561 (1995)

    PubMed  CAS  Google Scholar 

  17. N. Kokubu, M. Satoh, and I. Takayanagi, Involvement of botulinum C3-sensitive GTP-binding proteins in al-adrenoceptor subtypes Ca2+-sensitization, Eur. J. Pharmacol 290, 19–27 (1995)

    Article  PubMed  CAS  Google Scholar 

  18. A. Lucius, A. Anders, A. Steusloff, M. Troschka, F. Hofinan, K. Aktories, and G. Pfitzer, Clostridium difficile toxin B inhibits carbachol-induce force and myosin light chain phosphorylation in guinea-pig smooth muscle: role of Rho proteins, J. Physiol(Lond) 506, 83–93 (1998)

    Article  CAS  Google Scholar 

  19. M. Noda, C. Yasuda-Fukazawa, K. Moriishi, T. Kato, T. Okuda, K. Kurokawa, and Y. Takuwa, Involvement of Rho in GTPγS-induced enhancement of phosphorylation of 20 kDa myosin light chain in vascular smooth muscle cells: inhibition of phosphatase activity, FEBS Lett. 367, 246–250 (1995)

    Article  PubMed  CAS  Google Scholar 

  20. Y. Takuwa, M. Noda, C. Yasuda, M. Kumada, and K. Kurokawa, 1995, Regulation of Ca2+-dependent pholsphoaryttaion of 20kDa myosin light chain by the small molecular weight G protein Rho p21 in vascular smooth muscle cells, in: Regulation of the contractile cycle insmooth muscle edited by T. Nakano, D. J. Hartshome. Tokyo: Springer, pp. 103–110.

    Chapter  Google Scholar 

  21. Y. Takuwa, 1999, Regulation of smooth muscle myosin phosphatase and contraction by Rho and Rho kinase, in Molecular mechanisms of smooth muscle contraction, edited by K. Kohama and Y. Sasaki. Georgetown. R. G. Landes, pp. 47–58.

    Google Scholar 

  22. S, Narumiya, T. Ishizaki, and N. Watanabe, Rho effectoors and reorganization of actin cytoskeleton, FEBS. Lett. 410, 68–72 (1997)

    Article  PubMed  CAS  Google Scholar 

  23. L. Lim, E. Manser, T. Leung, and C. Hall, Regulation of phosphorylation pathways by p21 GTPases. The p21 Ras-related Rho subfamily and its role in phosphorylation signalling pathways, Eur. J. Biochem. 242, 171–185 (1996)

    Article  PubMed  CAS  Google Scholar 

  24. L. Van Aelst, and C. D. Souza-Schorey, Rho GTPases and signaling networks, Genes Dev. 11, 2295–2322 (1997)

    Article  PubMed  Google Scholar 

  25. K. Kimura, M. Ito, M. Amano, K. Chihara, Y. Fukata, M. Nakafuku, B. Yamamori, J. Feng, T. Nakano, K. Okawa, A. Iwamatsu, and K. Kaibuchi, Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase), Science 273, 245–248 (1996)

    Article  PubMed  CAS  Google Scholar 

  26. J. Feng, M. Ito, K. Ichikawa, M. Nishikawa, D. J. Hartshorne, and T. Nakano, Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase, J. Biol. Chem. 274, 37385–37390 (1999)

    Article  PubMed  CAS  Google Scholar 

  27. J. A. MacDonald, M. A. Borman, A. Muranyi, A. V. Somlyo, D. J. Hartshorne, and T. A. J. Haystead, Identification of the endogenous smooth muscle myosin phosphatase-associated kinase, Proc. Natl Acad. Sci. USA 98, 2419–2424 (2001)

    Article  PubMed  CAS  Google Scholar 

  28. Muranyi, J. A. MacDonald, J. T. Deng, D. P. Wilson, T. A. J. Haystead, M. P. Walsh, F. Erdodi, E. Kiss, Y. Wu, and D. J. Hartshorne, Phosphorylation of the myosin phosphatase target subunit by integrin-linked kinase, Biochem. J. 366, 211–216 (2002)

    PubMed  CAS  Google Scholar 

  29. M. Eto, T. Ohmori, M. Suzuki, K. Furuya, and F. Monta, A noved protein phosphatase1 inhibitory protein potentiated by protein kinase C isolated from porcine aorta media and characterization. J. Biochem. 118, 1104–1107 (1995)

    PubMed  CAS  Google Scholar 

  30. T. Kitazawa, M. Eto, T. P. Woodsome, and D. L. Brautigan, Agonist trigger G protein-mediated activation of the CPI-17 inhibitor phopsphoprotein of myosin light chain phosphatase to enhance cvascular smooth muscle contractility, J. Biol. Chem. 275, 9897–9900 (2000)

    Article  PubMed  CAS  Google Scholar 

  31. M. Koyama, M. Ito, J. Feng, T. Seko, K. Shiraki, K. Takase, D. J. Hartshorne, and T. Nakano, Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase by Rho kinase, FEBS Lett. 475, 197–200 (2000)

    Article  PubMed  CAS  Google Scholar 

  32. T. Hamaguchi, M. Ito, J. Feng, T. Seko, M. Koyama, H. Machida, K. Takase, M. Amano, K. Kaibuchi, D. J. Hartshorne, and T. Nakano, Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase by protein kinase N, Biochem. Biophys. Res. Commun. 214, 825–830 (2000)

    Article  Google Scholar 

  33. J. A. MacDonald, M. Eto, M. A. Borman, D. L. Brautigan, and T. A. J. Haystead, Dual Ser and Thr phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by MYPT-associated kinase, FEBS Lett. 493, 91–94 (2001)

    Article  PubMed  CAS  Google Scholar 

  34. J. T. Deng, C. Sutherland, D. L. Brautigan, M. Eto, and M. P. Walsh, Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase, Biochem. J. 367, 517–524 (2002)

    Article  PubMed  CAS  Google Scholar 

  35. M. Eto, T. Kitazawa, M. Yazawa, H.. Mukai, Y. Ono, and D. L. Brautigan, Histamine-induced vasoconstriction involves phosphorylation of a specific inhibitor protein for myosin phosphatase by protein kinase C alpha and delta isoforms, J. Biol Chem. 276, 29072–29078 (2001)

    Article  PubMed  CAS  Google Scholar 

  36. L. Bishop, and A. Hall, Rho GTPase and their effector proteins, Biochem. J. 348, 241–255 (2000)

    Article  PubMed  CAS  Google Scholar 

  37. S. Sakurada, H. Okamoto, N. Takuwa, N. Sugimoto, and Y. Takuwa, Rho activation in excitatory agonist-stimulated vascular smooth muscle, Am. J. Physiol 281, C571–C578 (2001)

    CAS  Google Scholar 

  38. Gohla, S. Offermanns, T. M. Wilkie, and G. Schultz, Differential involvement of Gα12 and Gαl3 in receptor-mediated stress fiber formation, J. Biol Chem. 274, 17901–17907 (1999)

    Article  PubMed  CAS  Google Scholar 

  39. S. Fukumoto, H. Chikumi, and J. S. Salvo, RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho, Oncogene 20, 1661–1668 (2001)

    Article  Google Scholar 

  40. M. A. Booden, D. P. Siderovski, and C. J. Der, Leukemia-associated Rho guanine nucleotide exchange factor promotes Gαq-coupled activation of RhoA, Mol. Cell. Biol. 22, 4053–4061 (2002)

    Article  PubMed  CAS  Google Scholar 

  41. H. Chikumi, J. Vazquez-Prado, J-M. Servitja, H. Miyazaki, and J. S. Gutkind, Potent activation of RhoA by Gαq and Gαq-coupled receptors, J. Biol. Chem. 277, 27130–27134 (2002)

    Article  PubMed  CAS  Google Scholar 

  42. Gohla, G. Schlutz, and S. Offermanns, Role for G12/13 in agonist-induced vascular smooth muscle cell contraction, Circ. Res. 87, 221–227 (2000)

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa, Japan, 920-8640

    Yoh Takuwa

Authors
  1. Yoh Takuwa
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Teikyo University, Tokyo, Japan

    Haruo Sugi

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this paper

Cite this paper

Takuwa, Y. (2003). Regulation of the RHO Signaling Pathway by Excitatory Agonists in Vascular Smooth Muscle. In: Sugi, H. (eds) Molecular and Cellular Aspects of Muscle Contraction. Advances in Experimental Medicine and Biology, vol 538. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9029-7_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9029-7_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4764-4

  • Online ISBN: 978-1-4419-9029-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation