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Actions downstream of cGMP/PKG can reverse PKC-mediated phosphorylation of CPI-17 and Ca2+ sensitization in smooth muscle.

Bonnevier, Johan LU and Arner, Anders LU (2004) In Journal of Biological Chemistry 279(24). p.28998-29003
Abstract
Ca2+ sensitivity of smooth muscle contraction is modulated by several systems converging on myosin light chain phosphatase (MLCP). Rho-Rho kinase is considered to inhibit MLCP via phosphorylation, whereas protein kinase C (PKC) induced sensitization has been shown to be dependent on phosphorylation of the inhibitory protein CPI-17. We have explored the interaction of cGMP-dependent protein kinase (PKG) with Ca2+ sensitization pathways using permeabilized mouse smooth muscle. Three conditions giving ~50% of maximal active force were compared in small intestinal preparations: 1) Ca2+-activated unsensitized muscle (pCa 5.9 with Rho kinase inhibitor Y27632); 2) Rho-Rho kinase-sensitized muscle (pCa 6.1 with guanosine... (More)
Ca2+ sensitivity of smooth muscle contraction is modulated by several systems converging on myosin light chain phosphatase (MLCP). Rho-Rho kinase is considered to inhibit MLCP via phosphorylation, whereas protein kinase C (PKC) induced sensitization has been shown to be dependent on phosphorylation of the inhibitory protein CPI-17. We have explored the interaction of cGMP-dependent protein kinase (PKG) with Ca2+ sensitization pathways using permeabilized mouse smooth muscle. Three conditions giving ~50% of maximal active force were compared in small intestinal preparations: 1) Ca2+-activated unsensitized muscle (pCa 5.9 with Rho kinase inhibitor Y27632); 2) Rho-Rho kinase-sensitized muscle (pCa 6.1 with guanosine 5'-3-O-(thio)triphosphate); and 3) PKC-sensitized muscle (pCa 6.0 with Y27632 and PKC activator phorbol 12,13-dibutyrate). 8-Br-cGMP relaxed the sensitized muscles but had marginal effects on unsensitized preparations, showing that PKG reverses both PKC and Rho-mediated Ca2+ sensitization. CPI-17 was present in permeabilized intestinal tissue. In PKC-sensitized preparations, CPI-17 phosphorylation decreased in response to 8-Br-cGMP. The rate of PKC-mediated phosphorylation in the presence of the MLCP inhibitor microcystin-LR was not influenced by 8-Br-cGMP. PKC-induced Ca2+ sensitization also was reversed in vascular smooth muscle tissues (portal vein and femoral artery). We conclude that actions downstream of cGMP/PKG can reverse PKC-mediated phosphorylation of CPI-17 and Ca2+ sensitization in smooth muscle. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
279
issue
24
pages
28998 - 29003
publisher
ASBMB
external identifiers
  • wos:000222445300022
  • scopus:3142675244
ISSN
1083-351X
DOI
10.1074/jbc.M404259200
language
English
LU publication?
yes
id
445f15e6-4ca1-4668-a570-f846a7568d5e (old id 123642)
date added to LUP
2007-07-10 14:41:50
date last changed
2017-07-09 03:40:03
@article{445f15e6-4ca1-4668-a570-f846a7568d5e,
  abstract     = {Ca2+ sensitivity of smooth muscle contraction is modulated by several systems converging on myosin light chain phosphatase (MLCP). Rho-Rho kinase is considered to inhibit MLCP via phosphorylation, whereas protein kinase C (PKC) induced sensitization has been shown to be dependent on phosphorylation of the inhibitory protein CPI-17. We have explored the interaction of cGMP-dependent protein kinase (PKG) with Ca2+ sensitization pathways using permeabilized mouse smooth muscle. Three conditions giving ~50% of maximal active force were compared in small intestinal preparations: 1) Ca2+-activated unsensitized muscle (pCa 5.9 with Rho kinase inhibitor Y27632); 2) Rho-Rho kinase-sensitized muscle (pCa 6.1 with guanosine 5'-3-O-(thio)triphosphate); and 3) PKC-sensitized muscle (pCa 6.0 with Y27632 and PKC activator phorbol 12,13-dibutyrate). 8-Br-cGMP relaxed the sensitized muscles but had marginal effects on unsensitized preparations, showing that PKG reverses both PKC and Rho-mediated Ca2+ sensitization. CPI-17 was present in permeabilized intestinal tissue. In PKC-sensitized preparations, CPI-17 phosphorylation decreased in response to 8-Br-cGMP. The rate of PKC-mediated phosphorylation in the presence of the MLCP inhibitor microcystin-LR was not influenced by 8-Br-cGMP. PKC-induced Ca2+ sensitization also was reversed in vascular smooth muscle tissues (portal vein and femoral artery). We conclude that actions downstream of cGMP/PKG can reverse PKC-mediated phosphorylation of CPI-17 and Ca2+ sensitization in smooth muscle.},
  author       = {Bonnevier, Johan and Arner, Anders},
  issn         = {1083-351X},
  language     = {eng},
  number       = {24},
  pages        = {28998--29003},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Actions downstream of cGMP/PKG can reverse PKC-mediated phosphorylation of CPI-17 and Ca2+ sensitization in smooth muscle.},
  url          = {http://dx.doi.org/10.1074/jbc.M404259200},
  volume       = {279},
  year         = {2004},
}