© 2000 American Heart Association, Inc.
Cellular Biology |
Role for G12/G13 in Agonist-Induced Vascular Smooth Muscle Cell Contraction
From the Institut für Pharmakologie (A.G., G.S., S.O.), Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany, and Pharmakologisches Institut (S.O.), Universität Heidelberg, Heidelberg, Germany. Dr Gohla is now at The Scripps Research Institute, La Jolla, Calif.
Correspondence to Dr Stefan Offermanns, Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany. E-mail stefan.offermanns{at}urz.uni-heidelberg.de
Abstract—Receptor-induced
vascular smooth muscle cell contraction is mediated by dual regulation
of myosin light chain (MLC20)
phosphorylation through Ca2+-dependent
stimulation of myosin light chain kinase and Rho/Rho-kinase–mediated
inhibition of myosin phosphatase. Although myosin light chain kinase
regulation is initiated by the coupling of receptors to G proteins of
the Gq family, Gq and G11, it is
not known how receptors regulate the Rho/Rho-kinase–mediated pathway.
In vascular smooth muscle cells, receptor-mediated MLC20
phosphorylation and cell contraction was blocked by
inhibitors of each of the pathways. Receptors of various
vasocontractors were found to couple to Gq/G11
and G12/G13, and constitutively active forms of
G
12 and G13 induced a pronounced
contraction of vascular smooth muscle cells that could be blocked by C3
exoenzyme, by inhibition of Rho-kinase, and by stable analogues of cGMP
and cAMP. Receptor-mediated smooth muscle cell contraction was strongly
inhibited by dominant-negative forms of G12 and
G13. These data indicate that a
G12/G13-mediated Rho/Rho-kinase–dependent
pathway operates in smooth muscle cells and that dual regulation of
MLC20 phosphorylation by vasocontractors is
initiated by the dual coupling of their receptors to G proteins of the
Gq and G12 families.
Key Words: smooth muscle • vasocontractors • G proteins • Rho-kinase • myosin light chain phosphorylation
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
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|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
Y. Kawanabe, Y. Okamoto, K. Nozaki, N. Hashimoto, S. Miwa, and T. Masaki Molecular Mechanism for Endothelin-1-Induced Stress-Fiber Formation: Analysis of G Proteins Using a Mutant EndothelinA Receptor Mol. Pharmacol., February 1, 2002; 61(2): 277 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
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|
|
|
|
|
|
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|
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|
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|
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