Molecular events associated with the regulation of signaling by M2
muscarinic receptors
M. Hosey, R. Pals-Rylaarsdam, K. Lee, A. Roseberry, J. Benovic, V. Gurevich, и M. Bunemann. Life Sci, 64 (6-7):
363-8(1999)Hosey, M M Pals-Rylaarsdam, R Lee, K B Roseberry, A G Benovic, J
L Gurevich, V V Bunemann, M EY11500/EY/NEI NIH HHS/United States
GM44944/GM/NIGMS NIH HHS/United States HL 50121/HL/NHLBI NIH HHS/United
States etc. Research Support, Non-U.S. Gov't Research Support, U.S.
Gov't, P.H.S. England Life sciences Life Sci. 1999;64(6-7):363-8..
Аннотация
Multiple events are associated with the regulation of signaling by
the M2 muscarinic cholinergic receptors (mAChRs). Desensitization
of the attenuation of adenylyl cyclase by the M2 mAChRs appears to
involve agonist-dependent phosphorylation of M2 mAChRs by G-protein
coupled receptor kinases (GRKs) that phosphorylate the receptors
in a serine/threonine rich motif in the 3rd intracellular domain
of the receptors. Mutation of residues 307-311 from TVSTS to AVAAA
in this domain of the human M2 mAChR results in a loss of receptor/G-protein
uncoupling and a loss of arrestin binding. Agonist-induced sequestration
of receptors away from their normal membrane environment is also
regulated by agonist-induced phosphorylation of the M2 mAChRs on
the 3rd intracellular domain, but in HEK cells, the predominant pathway
of internalization is not regulated by GRKs or arrestins. This pathway
of internalization is not inhibited by a dominant negative dynamin,
and does not appear to involve either clathrin coated pits or caveolae.
The signaling of the M2 mAChR to G-protein regulated inwardly rectifying
K channels (GIRKs) can be modified by RGS proteins. In HEK cells,
expression of RGS proteins leads to a constitutive activation of
the channels through a mechanism that depends on Gbetagamma. RGS
proteins appear to increase the concentration of free Gbetagamma
in addition to acting as GAPs. Thus multiple mechanisms acting at
either the level of the M2 mAChRs or the G-proteins can contribute
to the regulation of signaling via the M2 mAChRs.
Hosey, M M Pals-Rylaarsdam, R Lee, K B Roseberry, A G Benovic, J
L Gurevich, V V Bunemann, M EY11500/EY/NEI NIH HHS/United States
GM44944/GM/NIGMS NIH HHS/United States HL 50121/HL/NHLBI NIH HHS/United
States etc. Research Support, Non-U.S. Gov't Research Support, U.S.
Gov't, P.H.S. England Life sciences Life Sci. 1999;64(6-7):363-8.
%0 Journal Article
%1 Hosey1999
%A Hosey, M. M.
%A Pals-Rylaarsdam, R.
%A Lee, K. B.
%A Roseberry, A. G.
%A Benovic, J. L.
%A Gurevich, V. V.
%A Bunemann, M.
%D 1999
%J Life Sci
%K & *GTPase-Activating *Potassium *RGS *Signal AMP-Dependent Acid Adenylate Amino Arrestins/metabolism Barium/pharmacology Blockers Bordetella/pharmacology Carbachol/pharmacology Cell Channel Channels Channels, Channels/genetics/metabolism Cyclase Cyclic Dominant/genetics/physiology Down-Regulation/drug Factors, G GTP-Binding Genes, Humans Inwardly Inwardly-Rectifying Kinases Kinases/genetics/physiology Line M2 Muscarinic Muscarinic/genetics/*metabolism Phosphorylation Potassium Protein Protein-Coupled Proteins Proteins/antagonists Proteins/genetics/physiology Receptor Rectifying Substitution Toxin Transduction Transfection Virulence beta-Adrenergic effects inhibitors/*metabolism
%N 6-7
%P 363-8
%T Molecular events associated with the regulation of signaling by M2
muscarinic receptors
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10069497
%V 64
%X Multiple events are associated with the regulation of signaling by
the M2 muscarinic cholinergic receptors (mAChRs). Desensitization
of the attenuation of adenylyl cyclase by the M2 mAChRs appears to
involve agonist-dependent phosphorylation of M2 mAChRs by G-protein
coupled receptor kinases (GRKs) that phosphorylate the receptors
in a serine/threonine rich motif in the 3rd intracellular domain
of the receptors. Mutation of residues 307-311 from TVSTS to AVAAA
in this domain of the human M2 mAChR results in a loss of receptor/G-protein
uncoupling and a loss of arrestin binding. Agonist-induced sequestration
of receptors away from their normal membrane environment is also
regulated by agonist-induced phosphorylation of the M2 mAChRs on
the 3rd intracellular domain, but in HEK cells, the predominant pathway
of internalization is not regulated by GRKs or arrestins. This pathway
of internalization is not inhibited by a dominant negative dynamin,
and does not appear to involve either clathrin coated pits or caveolae.
The signaling of the M2 mAChR to G-protein regulated inwardly rectifying
K channels (GIRKs) can be modified by RGS proteins. In HEK cells,
expression of RGS proteins leads to a constitutive activation of
the channels through a mechanism that depends on Gbetagamma. RGS
proteins appear to increase the concentration of free Gbetagamma
in addition to acting as GAPs. Thus multiple mechanisms acting at
either the level of the M2 mAChRs or the G-proteins can contribute
to the regulation of signaling via the M2 mAChRs.
@article{Hosey1999,
abstract = {Multiple events are associated with the regulation of signaling by
the M2 muscarinic cholinergic receptors (mAChRs). Desensitization
of the attenuation of adenylyl cyclase by the M2 mAChRs appears to
involve agonist-dependent phosphorylation of M2 mAChRs by G-protein
coupled receptor kinases (GRKs) that phosphorylate the receptors
in a serine/threonine rich motif in the 3rd intracellular domain
of the receptors. Mutation of residues 307-311 from TVSTS to AVAAA
in this domain of the human M2 mAChR results in a loss of receptor/G-protein
uncoupling and a loss of arrestin binding. Agonist-induced sequestration
of receptors away from their normal membrane environment is also
regulated by agonist-induced phosphorylation of the M2 mAChRs on
the 3rd intracellular domain, but in HEK cells, the predominant pathway
of internalization is not regulated by GRKs or arrestins. This pathway
of internalization is not inhibited by a dominant negative dynamin,
and does not appear to involve either clathrin coated pits or caveolae.
The signaling of the M2 mAChR to G-protein regulated inwardly rectifying
K channels (GIRKs) can be modified by RGS proteins. In HEK cells,
expression of RGS proteins leads to a constitutive activation of
the channels through a mechanism that depends on Gbetagamma. RGS
proteins appear to increase the concentration of free Gbetagamma
in addition to acting as GAPs. Thus multiple mechanisms acting at
either the level of the M2 mAChRs or the G-proteins can contribute
to the regulation of signaling via the M2 mAChRs.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Hosey, M. M. and Pals-Rylaarsdam, R. and Lee, K. B. and Roseberry, A. G. and Benovic, J. L. and Gurevich, V. V. and Bunemann, M.},
biburl = {https://www.bibsonomy.org/bibtex/26c2d33f3a7de1241e41d522699a222b9/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {8912b4531fd79619ad7059b11e7090e0},
intrahash = {6c2d33f3a7de1241e41d522699a222b9},
issn = {0024-3205 (Print) 0024-3205 (Linking)},
journal = {Life Sci},
keywords = {& *GTPase-Activating *Potassium *RGS *Signal AMP-Dependent Acid Adenylate Amino Arrestins/metabolism Barium/pharmacology Blockers Bordetella/pharmacology Carbachol/pharmacology Cell Channel Channels Channels, Channels/genetics/metabolism Cyclase Cyclic Dominant/genetics/physiology Down-Regulation/drug Factors, G GTP-Binding Genes, Humans Inwardly Inwardly-Rectifying Kinases Kinases/genetics/physiology Line M2 Muscarinic Muscarinic/genetics/*metabolism Phosphorylation Potassium Protein Protein-Coupled Proteins Proteins/antagonists Proteins/genetics/physiology Receptor Rectifying Substitution Toxin Transduction Transfection Virulence beta-Adrenergic effects inhibitors/*metabolism},
note = {Hosey, M M Pals-Rylaarsdam, R Lee, K B Roseberry, A G Benovic, J
L Gurevich, V V Bunemann, M EY11500/EY/NEI NIH HHS/United States
GM44944/GM/NIGMS NIH HHS/United States HL 50121/HL/NHLBI NIH HHS/United
States etc. Research Support, Non-U.S. Gov't Research Support, U.S.
Gov't, P.H.S. England Life sciences Life Sci. 1999;64(6-7):363-8.},
number = {6-7},
pages = {363-8},
shorttitle = {Molecular events associated with the regulation of signaling by M2
muscarinic receptors},
timestamp = {2010-12-14T18:20:21.000+0100},
title = {Molecular events associated with the regulation of signaling by M2
muscarinic receptors},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10069497},
volume = 64,
year = 1999
}