Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell
contraction
A. Gohla, G. Schultz, and S. Offermanns. Circ Res, 87 (3):
221-7(August 2000)Gohla, A Schultz, G Offermanns, S Research Support, Non-U.S. Gov't
United states Circulation research Circ Res. 2000 Aug 4;87(3):221-7..
Abstract
Receptor-induced vascular smooth muscle cell contraction is mediated
by dual regulation of myosin light chain (MLC(20)) phosphorylation
through Ca(2+)-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 G(q) family, G(q) and G(11), it
is not known how receptors regulate the Rho/Rho-kinase-mediated pathway.
In vascular smooth muscle cells, receptor-mediated MLC(20) phosphorylation
and cell contraction was blocked by inhibitors of each of the pathways.
Receptors of various vasocontractors were found to couple to G(q)/G(11)
and G(12)/G(13), and constitutively active forms of G alpha(12) and
G alpha(13) 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 G alpha(12) and G alpha(13). These data indicate that a
G(12)/G(13)-mediated Rho/Rho-kinase-dependent pathway operates in
smooth muscle cells and that dual regulation of MLC(20) phosphorylation
by vasocontractors is initiated by the dual coupling of their receptors
to G proteins of the G(q) and G(12) families.
%0 Journal Article
%1 Gohla2000
%A Gohla, A.
%A Schultz, G.
%A Offermanns, S.
%D 2000
%J Circ Res
%K & *GTP-Binding A Agents/*pharmacology Animals Biological Calcium Chains/metabolism Endothelin Endothelin-1/*pharmacology Endothelin/*drug G12-G13 GTP-Binding Gi-Go Gi2 Gohla Heterotrimeric Intracellular Kinase/metabolism Kinases Kinases/antagonists Light Models, Muscle, Myosin Myosin-Light-Chain Peptides Phosphorylation Post-Translational Processing, Protein Protein-Serine-Threonine Protein/*physiology Proteins Proteins/*physiology Proto-Oncogene Signal Signaling Signaling/physiology Smooth, Subunit, Subunits, Transduction/physiology Vascular/cytology/*drug Vasoconstriction/drug Vasoconstrictor alpha and effects/*physiology effects/physiology inhibitors/*physiology rho-Associated rhoA Receptor
%N 3
%P 221-7
%T Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell
contraction
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10926873
%V 87
%X Receptor-induced vascular smooth muscle cell contraction is mediated
by dual regulation of myosin light chain (MLC(20)) phosphorylation
through Ca(2+)-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 G(q) family, G(q) and G(11), it
is not known how receptors regulate the Rho/Rho-kinase-mediated pathway.
In vascular smooth muscle cells, receptor-mediated MLC(20) phosphorylation
and cell contraction was blocked by inhibitors of each of the pathways.
Receptors of various vasocontractors were found to couple to G(q)/G(11)
and G(12)/G(13), and constitutively active forms of G alpha(12) and
G alpha(13) 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 G alpha(12) and G alpha(13). These data indicate that a
G(12)/G(13)-mediated Rho/Rho-kinase-dependent pathway operates in
smooth muscle cells and that dual regulation of MLC(20) phosphorylation
by vasocontractors is initiated by the dual coupling of their receptors
to G proteins of the G(q) and G(12) families.
@article{Gohla2000,
abstract = {Receptor-induced vascular smooth muscle cell contraction is mediated
by dual regulation of myosin light chain (MLC(20)) phosphorylation
through Ca(2+)-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 G(q) family, G(q) and G(11), it
is not known how receptors regulate the Rho/Rho-kinase-mediated pathway.
In vascular smooth muscle cells, receptor-mediated MLC(20) phosphorylation
and cell contraction was blocked by inhibitors of each of the pathways.
Receptors of various vasocontractors were found to couple to G(q)/G(11)
and G(12)/G(13), and constitutively active forms of G alpha(12) and
G alpha(13) 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 G alpha(12) and G alpha(13). These data indicate that a
G(12)/G(13)-mediated Rho/Rho-kinase-dependent pathway operates in
smooth muscle cells and that dual regulation of MLC(20) phosphorylation
by vasocontractors is initiated by the dual coupling of their receptors
to G proteins of the G(q) and G(12) families.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Gohla, A. and Schultz, G. and Offermanns, S.},
biburl = {https://www.bibsonomy.org/bibtex/2a0c94dfcda5f1df6ebac36d961f4aa5b/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {b047dd878cdfcff7005c5dec0f287353},
intrahash = {a0c94dfcda5f1df6ebac36d961f4aa5b},
issn = {0009-7330 (Print) 0009-7330 (Linking)},
journal = {Circ Res},
keywords = {& *GTP-Binding A Agents/*pharmacology Animals Biological Calcium Chains/metabolism Endothelin Endothelin-1/*pharmacology Endothelin/*drug G12-G13 GTP-Binding Gi-Go Gi2 Gohla Heterotrimeric Intracellular Kinase/metabolism Kinases Kinases/antagonists Light Models, Muscle, Myosin Myosin-Light-Chain Peptides Phosphorylation Post-Translational Processing, Protein Protein-Serine-Threonine Protein/*physiology Proteins Proteins/*physiology Proto-Oncogene Signal Signaling Signaling/physiology Smooth, Subunit, Subunits, Transduction/physiology Vascular/cytology/*drug Vasoconstriction/drug Vasoconstrictor alpha and effects/*physiology effects/physiology inhibitors/*physiology rho-Associated rhoA Receptor},
month = {Aug 4},
note = {Gohla, A Schultz, G Offermanns, S Research Support, Non-U.S. Gov't
United states Circulation research Circ Res. 2000 Aug 4;87(3):221-7.},
number = 3,
pages = {221-7},
shorttitle = {Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell
contraction},
timestamp = {2010-12-14T18:22:02.000+0100},
title = {Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell
contraction},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10926873},
volume = 87,
year = 2000
}