Overexpression of beta-arrestin and beta-adrenergic receptor kinase
augment desensitization of beta 2-adrenergic receptors
S. Pippig, S. Andexinger, K. Daniel, M. Puzicha, M. Caron, R. Lefkowitz, and M. Lohse. J Biol Chem, 268 (5):
3201-8(February 1993)Pippig, S Andexinger, S Daniel, K Puzicha, M Caron, M G Lefkowitz,
R J Lohse, M J Research Support, Non-U.S. Gov't United states The
Journal of biological chemistry J Biol Chem. 1993 Feb 15;268(5):3201-8..
Abstract
Receptor-specific or homologous desensitization of beta 2-adrenergic
receptors is thought to be effected via phosphorylation of the receptor
by the beta-adrenergic receptor kinase (beta ARK), followed by binding
of beta-arrestin. We have generated stably transfected Chinese hamster
ovary cell lines overexpressing either of the two regulatory proteins
and also expressing low or high levels of beta 2-adrenergic receptors
(approximately 80 and approximately 600 fmol/mg of membrane protein).
In these cells, we studied the process of desensitization induced
by the beta-adrenergic receptor agonist isoproterenol. In cells expressing
high levels of beta 2-adrenergic receptors, desensitization to high
concentrations of isoproterenol (previously shown to be mediated
by both beta ARK and protein kinase A) amounted to approximately
50% in control cells, approximately 80% in beta ARK-overexpressing
cells, and approximately 90% in beta-arrestin-overexpressing cells.
In cells expressing low levels of beta 2-adrenergic receptors, these
values were approximately 50, approximately 60, and approximately
60%, respectively. Desensitization to low concentrations of isoproterenol
(previously shown to be essentially protein kinase A-mediated and
not receptor-specific, i.e. heterologous) was not affected by overexpression
of either beta ARK or beta-arrestin. These data suggest that in cells
expressing high levels of beta 2-adrenergic receptors, beta-arrestin
and beta ARK become limiting for homologous receptor desensitization.
They provide further support for the involvement of these two proteins
in the regulation of beta 2-adrenergic receptor function.
Pippig, S Andexinger, S Daniel, K Puzicha, M Caron, M G Lefkowitz,
R J Lohse, M J Research Support, Non-U.S. Gov't United states The
Journal of biological chemistry J Biol Chem. 1993 Feb 15;268(5):3201-8.
%0 Journal Article
%1 Pippig1993
%A Pippig, S.
%A Andexinger, S.
%A Daniel, K.
%A Puzicha, M.
%A Caron, M. G.
%A Lefkowitz, R. J.
%A Lohse, M. J.
%D 1993
%J J Biol Chem
%K & *Arrestins *Cyclic 5'-O-(3-Thiotriphosphate)/pharmacology AMP-Dependent Acid Adenylate Amino Animals Antibodies Antigens/genetics/*metabolism Blotting, CHO Cell Chloride/pharmacology Cricetinae Cyclase/metabolism Data Eye GTP Guanosine Iodine Iodocyanopindolol Isoproterenol/*pharmacology Kinases Kinases/genetics/*metabolism Kinetics Line Magnesium Molecular Peptides/chemical Phosphohydrolases/metabolism Phosphorus Pindolol/analogs Protein Proteins/genetics/*metabolism Radioisotopes Radioisotopes/metabolism Receptor Sequence Transfection Western beta-Adrenergic beta/*drug derivatives/metabolism effects/metabolism synthesis/immunology Adrenergic
%N 5
%P 3201-8
%T Overexpression of beta-arrestin and beta-adrenergic receptor kinase
augment desensitization of beta 2-adrenergic receptors
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8381421
%V 268
%X Receptor-specific or homologous desensitization of beta 2-adrenergic
receptors is thought to be effected via phosphorylation of the receptor
by the beta-adrenergic receptor kinase (beta ARK), followed by binding
of beta-arrestin. We have generated stably transfected Chinese hamster
ovary cell lines overexpressing either of the two regulatory proteins
and also expressing low or high levels of beta 2-adrenergic receptors
(approximately 80 and approximately 600 fmol/mg of membrane protein).
In these cells, we studied the process of desensitization induced
by the beta-adrenergic receptor agonist isoproterenol. In cells expressing
high levels of beta 2-adrenergic receptors, desensitization to high
concentrations of isoproterenol (previously shown to be mediated
by both beta ARK and protein kinase A) amounted to approximately
50% in control cells, approximately 80% in beta ARK-overexpressing
cells, and approximately 90% in beta-arrestin-overexpressing cells.
In cells expressing low levels of beta 2-adrenergic receptors, these
values were approximately 50, approximately 60, and approximately
60%, respectively. Desensitization to low concentrations of isoproterenol
(previously shown to be essentially protein kinase A-mediated and
not receptor-specific, i.e. heterologous) was not affected by overexpression
of either beta ARK or beta-arrestin. These data suggest that in cells
expressing high levels of beta 2-adrenergic receptors, beta-arrestin
and beta ARK become limiting for homologous receptor desensitization.
They provide further support for the involvement of these two proteins
in the regulation of beta 2-adrenergic receptor function.
@article{Pippig1993,
abstract = {Receptor-specific or homologous desensitization of beta 2-adrenergic
receptors is thought to be effected via phosphorylation of the receptor
by the beta-adrenergic receptor kinase (beta ARK), followed by binding
of beta-arrestin. We have generated stably transfected Chinese hamster
ovary cell lines overexpressing either of the two regulatory proteins
and also expressing low or high levels of beta 2-adrenergic receptors
(approximately 80 and approximately 600 fmol/mg of membrane protein).
In these cells, we studied the process of desensitization induced
by the beta-adrenergic receptor agonist isoproterenol. In cells expressing
high levels of beta 2-adrenergic receptors, desensitization to high
concentrations of isoproterenol (previously shown to be mediated
by both beta ARK and protein kinase A) amounted to approximately
50% in control cells, approximately 80% in beta ARK-overexpressing
cells, and approximately 90% in beta-arrestin-overexpressing cells.
In cells expressing low levels of beta 2-adrenergic receptors, these
values were approximately 50, approximately 60, and approximately
60%, respectively. Desensitization to low concentrations of isoproterenol
(previously shown to be essentially protein kinase A-mediated and
not receptor-specific, i.e. heterologous) was not affected by overexpression
of either beta ARK or beta-arrestin. These data suggest that in cells
expressing high levels of beta 2-adrenergic receptors, beta-arrestin
and beta ARK become limiting for homologous receptor desensitization.
They provide further support for the involvement of these two proteins
in the regulation of beta 2-adrenergic receptor function.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Pippig, S. and Andexinger, S. and Daniel, K. and Puzicha, M. and Caron, M. G. and Lefkowitz, R. J. and Lohse, M. J.},
biburl = {https://www.bibsonomy.org/bibtex/2884bfa27941462577d9c46d1a115dc4b/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {257a77fbdfad6240bd1f05d1394f6c94},
intrahash = {884bfa27941462577d9c46d1a115dc4b},
issn = {0021-9258 (Print) 0021-9258 (Linking)},
journal = {J Biol Chem},
keywords = {& *Arrestins *Cyclic 5'-O-(3-Thiotriphosphate)/pharmacology AMP-Dependent Acid Adenylate Amino Animals Antibodies Antigens/genetics/*metabolism Blotting, CHO Cell Chloride/pharmacology Cricetinae Cyclase/metabolism Data Eye GTP Guanosine Iodine Iodocyanopindolol Isoproterenol/*pharmacology Kinases Kinases/genetics/*metabolism Kinetics Line Magnesium Molecular Peptides/chemical Phosphohydrolases/metabolism Phosphorus Pindolol/analogs Protein Proteins/genetics/*metabolism Radioisotopes Radioisotopes/metabolism Receptor Sequence Transfection Western beta-Adrenergic beta/*drug derivatives/metabolism effects/metabolism synthesis/immunology Adrenergic},
month = {Feb 15},
note = {Pippig, S Andexinger, S Daniel, K Puzicha, M Caron, M G Lefkowitz,
R J Lohse, M J Research Support, Non-U.S. Gov't United states The
Journal of biological chemistry J Biol Chem. 1993 Feb 15;268(5):3201-8.},
number = 5,
pages = {3201-8},
shorttitle = {Overexpression of beta-arrestin and beta-adrenergic receptor kinase
augment desensitization of beta 2-adrenergic receptors},
timestamp = {2010-12-14T18:22:42.000+0100},
title = {Overexpression of beta-arrestin and beta-adrenergic receptor kinase
augment desensitization of beta 2-adrenergic receptors},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8381421},
volume = 268,
year = 1993
}