Journal of Muscle Research & Cell Motility

, Volume 25, Issue 8, pp 657–665 | Cite as

Telokin mediates Ca2+-desensitization through activation of myosin phosphatase in phasic and tonic smooth muscle

  • Nandini Choudhury
  • Alexander S. Khromov
  • Andrew P. Somlyo
  • Avril V. Somlyo
Article
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Abstract

Telokin, a 17 kDa smooth muscle specific protein, consists of the C-terminal domain of MLCK, is phosphorylated by PKA and PKG at Ser13 in vivo (Wu et al. (1998) J Biol Chem 273: 11362–11369; Walker et al. (2001) J. Biol Chem 276: 24519–24524) and is proposed to induce Ca2+-desensitization through activation of myosin phosphatase (Wu et al. (1998) J. Biol Chem 273: 11362–11369). Telokin is reported to be highly expressed in phasic with only trace amounts in tonic smooth muscle. In α-toxin permeabilized femoral artery, 5 μM 8-Br-cGMP induced a two-fold increase in telokin phosphorylation and a maximal 30% relaxation of Ca2+-activated force compared to a 90% relaxation in phasic ileum muscle consistent with the relative amounts of telokin expressed in ileum, 27 ± 4.6 μM SEM compared to 6 ± 1.7 μM SEM, in femoral artery. Recombinant Wt telokin and the phospho-telokin mutant, S13D relaxed telokin-depleted femoral artery, by 38 ± 8% SEM and 60 ± 20% SEM, respectively. 8-Br-cGMP increased the rate and decreased the amplitude of force development initiated by photolysis of caged ATP in α-toxin permeabilized ileum and femoral artery smooth muscle, consistent with a cGMP-induced increase in phosphatase activity. Similarly, in telokin depleted ileum, recombinant S13D mutant telokin significantly increased the rate (0.08 ± 0.01 s−1 vs. 014 ± 0.02 s−1) and decreased force amplitude. In conclusion, our data support a role for telokin in cyclic nucleotide-induced relaxation of not only phasic, but also tonic smooth muscle and that this relaxation is mediated by activation of myosin phosphatase activity leading to a decrease in myosin light chain phosphorylation.

Keywords

Cage Smooth Muscle Light Chain Femoral Artery Phosphatase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer 2005

Authors and Affiliations

  • Nandini Choudhury
    • 1
  • Alexander S. Khromov
    • 1
  • Andrew P. Somlyo
    • 1
  • Avril V. Somlyo
    • 1
  1. 1.Departments of Molecular Physiology and Biological Physics, Health Sciences SystemUniversity of VirginiaCharlottesvilleUSA

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