Beta-arrestin binding to the beta2-adrenergic receptor requires both
receptor phosphorylation and receptor activation
C. Krasel, M. Bunemann, K. Lorenz, and M. Lohse. J Biol Chem, 280 (10):
9528-35(March 2005)Krasel, Cornelius Bunemann, Moritz Lorenz, Kristina Lohse, Martin
J Research Support, Non-U.S. Gov't United States The Journal of biological
chemistry J Biol Chem. 2005 Mar 11;280(10):9528-35. Epub 2005 Jan
5..
Abstract
Homologous desensitization of beta2-adrenergic receptors has been
shown to be mediated by phosphorylation of the agonist-stimulated
receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by
binding of beta-arrestins to the phosphorylated receptor. Binding
of beta-arrestin to the receptor is a prerequisite for subsequent
receptor desensitization, internalization via clathrin-coated pits,
and the initiation of alternative signaling pathways. In this study
we have investigated the interactions between receptors and beta-arrestin2
in living cells using fluorescence resonance energy transfer. We
show that (a) the initial kinetics of beta-arrestin2 binding to the
receptor is limited by the kinetics of GRK2-mediated receptor phosphorylation;
(b) repeated stimulation leads to the accumulation of GRK2-phosphorylated
receptor, which can bind beta-arrestin2 very rapidly; and (c) the
interaction of beta-arrestin2 with the receptor depends on the activation
of the receptor by agonist because agonist withdrawal leads to swift
dissociation of the receptor-beta-arrestin2 complex. This fast agonist-controlled
association and dissociation of beta-arrestins from prephosphorylated
receptors should permit rapid control of receptor sensitivity in
repeatedly stimulated cells such as neurons.
Krasel, Cornelius Bunemann, Moritz Lorenz, Kristina Lohse, Martin
J Research Support, Non-U.S. Gov't United States The Journal of biological
chemistry J Biol Chem. 2005 Mar 11;280(10):9528-35. Epub 2005 Jan
5.
%0 Journal Article
%1 Krasel2005
%A Krasel, C.
%A Bunemann, M.
%A Lorenz, K.
%A Lohse, M. J.
%D 2005
%J J Biol Chem
%K 3 AMP-Dependent Animals Arrestins/*metabolism Cell Cyclic G-Protein-Coupled Humans Kidney Kinase Kinases Kinases/*metabolism Kinetics Line Mice Phosphorylation Protein Proteins/metabolism Receptor Recombinant Transfection beta-2/*metabolism beta-Adrenergic Adrenergic
%N 10
%P 9528-35
%T Beta-arrestin binding to the beta2-adrenergic receptor requires both
receptor phosphorylation and receptor activation
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15634674
%V 280
%X Homologous desensitization of beta2-adrenergic receptors has been
shown to be mediated by phosphorylation of the agonist-stimulated
receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by
binding of beta-arrestins to the phosphorylated receptor. Binding
of beta-arrestin to the receptor is a prerequisite for subsequent
receptor desensitization, internalization via clathrin-coated pits,
and the initiation of alternative signaling pathways. In this study
we have investigated the interactions between receptors and beta-arrestin2
in living cells using fluorescence resonance energy transfer. We
show that (a) the initial kinetics of beta-arrestin2 binding to the
receptor is limited by the kinetics of GRK2-mediated receptor phosphorylation;
(b) repeated stimulation leads to the accumulation of GRK2-phosphorylated
receptor, which can bind beta-arrestin2 very rapidly; and (c) the
interaction of beta-arrestin2 with the receptor depends on the activation
of the receptor by agonist because agonist withdrawal leads to swift
dissociation of the receptor-beta-arrestin2 complex. This fast agonist-controlled
association and dissociation of beta-arrestins from prephosphorylated
receptors should permit rapid control of receptor sensitivity in
repeatedly stimulated cells such as neurons.
@article{Krasel2005,
abstract = {Homologous desensitization of beta2-adrenergic receptors has been
shown to be mediated by phosphorylation of the agonist-stimulated
receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by
binding of beta-arrestins to the phosphorylated receptor. Binding
of beta-arrestin to the receptor is a prerequisite for subsequent
receptor desensitization, internalization via clathrin-coated pits,
and the initiation of alternative signaling pathways. In this study
we have investigated the interactions between receptors and beta-arrestin2
in living cells using fluorescence resonance energy transfer. We
show that (a) the initial kinetics of beta-arrestin2 binding to the
receptor is limited by the kinetics of GRK2-mediated receptor phosphorylation;
(b) repeated stimulation leads to the accumulation of GRK2-phosphorylated
receptor, which can bind beta-arrestin2 very rapidly; and (c) the
interaction of beta-arrestin2 with the receptor depends on the activation
of the receptor by agonist because agonist withdrawal leads to swift
dissociation of the receptor-beta-arrestin2 complex. This fast agonist-controlled
association and dissociation of beta-arrestins from prephosphorylated
receptors should permit rapid control of receptor sensitivity in
repeatedly stimulated cells such as neurons.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Krasel, C. and Bunemann, M. and Lorenz, K. and Lohse, M. J.},
biburl = {https://www.bibsonomy.org/bibtex/206a7b46cf3bb5509d8a29fc3bb6d2501/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {6456013f408cfd8833b98c4b1db86fdd},
intrahash = {06a7b46cf3bb5509d8a29fc3bb6d2501},
issn = {0021-9258 (Print) 0021-9258 (Linking)},
journal = {J Biol Chem},
keywords = {3 AMP-Dependent Animals Arrestins/*metabolism Cell Cyclic G-Protein-Coupled Humans Kidney Kinase Kinases Kinases/*metabolism Kinetics Line Mice Phosphorylation Protein Proteins/metabolism Receptor Recombinant Transfection beta-2/*metabolism beta-Adrenergic Adrenergic},
month = {Mar 11},
note = {Krasel, Cornelius Bunemann, Moritz Lorenz, Kristina Lohse, Martin
J Research Support, Non-U.S. Gov't United States The Journal of biological
chemistry J Biol Chem. 2005 Mar 11;280(10):9528-35. Epub 2005 Jan
5.},
number = 10,
pages = {9528-35},
shorttitle = {Beta-arrestin binding to the beta2-adrenergic receptor requires both
receptor phosphorylation and receptor activation},
timestamp = {2010-12-14T18:22:40.000+0100},
title = {Beta-arrestin binding to the beta2-adrenergic receptor requires both
receptor phosphorylation and receptor activation},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15634674},
volume = 280,
year = 2005
}