Dual role of the beta2-adrenergic receptor C terminus for the binding
of beta-arrestin and receptor internalization
C. Krasel, U. Zabel, K. Lorenz, S. Reiner, S. Al-Sabah, и M. Lohse. J Biol Chem, 283 (46):
31840-8(ноября 2008)Krasel, Cornelius Zabel, Ulrike Lorenz, Kristina Reiner, Susanne
Al-Sabah, Suleiman Lohse, Martin J BB/D012902/1/Biotechnology and
Biological Sciences Research Council/United Kingdom Research Support,
Non-U.S. Gov't United States The Journal of biological chemistry
J Biol Chem. 2008 Nov 14;283(46):31840-8. Epub 2008 Sep 18..
Аннотация
Homologous desensitization of beta2-adrenergic and other G-protein-coupled
receptors is a two-step process. After phosphorylation of agonist-occupied
receptors by G-protein-coupled receptor kinases, they bind beta-arrestins,
which triggers desensitization and internalization of the receptors.
Because it is not known which regions of the receptor are recognized
by beta-arrestins, we have investigated beta-arrestin interaction
and internalization of a set of mutants of the human beta2-adrenergic
receptor. Mutation of the four serine/threonine residues between
residues 355 and 364 led to the loss of agonist-induced receptor-beta-arrestin2
interaction as revealed by fluorescence resonance energy transfer
(FRET), translocation of beta-arrestin2 to the plasma membrane, and
receptor internalization. Mutation of all seven serine/threonine
residues distal to residue 381 did not affect agonist-induced receptor
internalization and beta-arrestin2 translocation. A beta2-adrenergic
receptor truncated distal to residue 381 interacted normally with
beta-arrestin2, whereas its ability to internalize in an agonist-dependent
manner was compromised. A similar impairment of internalization was
observed when only the last eight residues of the C terminus were
deleted. Our experiments show that the C terminus distal to residue
381 does not affect the initial interaction between receptor and
beta-arrestin, but its last eight amino acids facilitate receptor
internalization in concert with beta-arrestin2.
Krasel, Cornelius Zabel, Ulrike Lorenz, Kristina Reiner, Susanne
Al-Sabah, Suleiman Lohse, Martin J BB/D012902/1/Biotechnology and
Biological Sciences Research Council/United Kingdom Research Support,
Non-U.S. Gov't United States The Journal of biological chemistry
J Biol Chem. 2008 Nov 14;283(46):31840-8. Epub 2008 Sep 18.
%0 Journal Article
%1 Krasel2008
%A Krasel, C.
%A Zabel, U.
%A Lorenz, K.
%A Reiner, S.
%A Al-Sabah, S.
%A Lohse, M. J.
%D 2008
%J J Biol Chem
%K Acid Alignment Amino Arrestins/*metabolism Binding Cell Data Humans Kinetics Ligands Line Molecular Mutation/genetics Phosphorylation Protein Sequence Transport beta-2/chemistry/genetics/*metabolism Receptor Adrenergic
%N 46
%P 31840-8
%T Dual role of the beta2-adrenergic receptor C terminus for the binding
of beta-arrestin and receptor internalization
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18801735
%V 283
%X Homologous desensitization of beta2-adrenergic and other G-protein-coupled
receptors is a two-step process. After phosphorylation of agonist-occupied
receptors by G-protein-coupled receptor kinases, they bind beta-arrestins,
which triggers desensitization and internalization of the receptors.
Because it is not known which regions of the receptor are recognized
by beta-arrestins, we have investigated beta-arrestin interaction
and internalization of a set of mutants of the human beta2-adrenergic
receptor. Mutation of the four serine/threonine residues between
residues 355 and 364 led to the loss of agonist-induced receptor-beta-arrestin2
interaction as revealed by fluorescence resonance energy transfer
(FRET), translocation of beta-arrestin2 to the plasma membrane, and
receptor internalization. Mutation of all seven serine/threonine
residues distal to residue 381 did not affect agonist-induced receptor
internalization and beta-arrestin2 translocation. A beta2-adrenergic
receptor truncated distal to residue 381 interacted normally with
beta-arrestin2, whereas its ability to internalize in an agonist-dependent
manner was compromised. A similar impairment of internalization was
observed when only the last eight residues of the C terminus were
deleted. Our experiments show that the C terminus distal to residue
381 does not affect the initial interaction between receptor and
beta-arrestin, but its last eight amino acids facilitate receptor
internalization in concert with beta-arrestin2.
@article{Krasel2008,
abstract = {Homologous desensitization of beta2-adrenergic and other G-protein-coupled
receptors is a two-step process. After phosphorylation of agonist-occupied
receptors by G-protein-coupled receptor kinases, they bind beta-arrestins,
which triggers desensitization and internalization of the receptors.
Because it is not known which regions of the receptor are recognized
by beta-arrestins, we have investigated beta-arrestin interaction
and internalization of a set of mutants of the human beta2-adrenergic
receptor. Mutation of the four serine/threonine residues between
residues 355 and 364 led to the loss of agonist-induced receptor-beta-arrestin2
interaction as revealed by fluorescence resonance energy transfer
(FRET), translocation of beta-arrestin2 to the plasma membrane, and
receptor internalization. Mutation of all seven serine/threonine
residues distal to residue 381 did not affect agonist-induced receptor
internalization and beta-arrestin2 translocation. A beta2-adrenergic
receptor truncated distal to residue 381 interacted normally with
beta-arrestin2, whereas its ability to internalize in an agonist-dependent
manner was compromised. A similar impairment of internalization was
observed when only the last eight residues of the C terminus were
deleted. Our experiments show that the C terminus distal to residue
381 does not affect the initial interaction between receptor and
beta-arrestin, but its last eight amino acids facilitate receptor
internalization in concert with beta-arrestin2.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Krasel, C. and Zabel, U. and Lorenz, K. and Reiner, S. and Al-Sabah, S. and Lohse, M. J.},
biburl = {https://www.bibsonomy.org/bibtex/208c05834937c2a7fa7f0d211e1a6aa61/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {a64271d071e383776c8d4e2e93ef35eb},
intrahash = {08c05834937c2a7fa7f0d211e1a6aa61},
issn = {0021-9258 (Print) 0021-9258 (Linking)},
journal = {J Biol Chem},
keywords = {Acid Alignment Amino Arrestins/*metabolism Binding Cell Data Humans Kinetics Ligands Line Molecular Mutation/genetics Phosphorylation Protein Sequence Transport beta-2/chemistry/genetics/*metabolism Receptor Adrenergic},
month = {Nov 14},
note = {Krasel, Cornelius Zabel, Ulrike Lorenz, Kristina Reiner, Susanne
Al-Sabah, Suleiman Lohse, Martin J BB/D012902/1/Biotechnology and
Biological Sciences Research Council/United Kingdom Research Support,
Non-U.S. Gov't United States The Journal of biological chemistry
J Biol Chem. 2008 Nov 14;283(46):31840-8. Epub 2008 Sep 18.},
number = 46,
pages = {31840-8},
shorttitle = {Dual role of the beta2-adrenergic receptor C terminus for the binding
of beta-arrestin and receptor internalization},
timestamp = {2010-12-14T18:22:40.000+0100},
title = {Dual role of the beta2-adrenergic receptor C terminus for the binding
of beta-arrestin and receptor internalization},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18801735},
volume = 283,
year = 2008
}