%0 Journal Article %1 Benovic1990 %A Benovic, J. L. %A Onorato, J. %A Lohse, M. J. %A Dohlman, H. G. %A Staniszewski, C. %A Caron, M. G. %A Lefkowitz, R. J. %D 1990 %J Br J Clin Pharmacol %K AMP-Dependent Acid Amino Animals Cricetinae Cyclic Data Electrophoresis, GTP-Binding Gel Inhibitors Kinase Kinases Kinases/isolation Kinetics Molecular Peptides/chemical Phosphorylation Polyacrylamide Protein Proteins/metabolism Receptor Sequence Specificity Substrate beta-Adrenergic beta/*chemistry/metabolism purification/*metabolism synthesis/*metabolism/pharmacology Adrenergic %P 3S-12S %T Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2176526 %V 30 Suppl 1 %X 1. The beta-adrenoceptor is one of a number of G protein-coupled receptors which have been proposed to contain seven transmembrane alpha-helices. The function of this receptor appears to be regulated by phosphorylation by a specific enzyme, the beta-adrenoceptor kinase. Synthetic peptides which comprise each of the proposed intra- and extracellular domains of the beta 2-adrenoceptor have been tested as potential substrates and inhibitors of the beta-adrenoceptor kinase. 2. Two peptides which encompass the middle and terminal portions of the carboxyl tail of the receptor served as substrates by beta-adrenoceptor kinase. The kinetics of the phosphorylation reaction, however, suggest that these peptides are 10(6)-fold poorer substrate than the agonist occupied receptor. 3. A number of synthetic peptides also served as inhibitors of beta 2-adrenoceptor phosphorylation by beta-adrenoceptor kinase. In particular, a peptide which comprised the first intracellular loop of the beta 2-adrenoceptor (amino acids 56-74) inhibited most effectively with an IC50 of 40 microM. 4. These results suggest that multiple intracellular regions of the beta-receptor may serve as potential sites of interaction with beta-adrenoceptor kinase. Moreover, these regions may serve as potential targets for the development of specific inhibitors of beta-adrenoceptor kinase which could be used to block homologous desensitization.

@article{Benovic1990, abstract = {1. The beta-adrenoceptor is one of a number of G protein-coupled receptors which have been proposed to contain seven transmembrane alpha-helices. The function of this receptor appears to be regulated by phosphorylation by a specific enzyme, the beta-adrenoceptor kinase. Synthetic peptides which comprise each of the proposed intra- and extracellular domains of the beta 2-adrenoceptor have been tested as potential substrates and inhibitors of the beta-adrenoceptor kinase. 2. Two peptides which encompass the middle and terminal portions of the carboxyl tail of the receptor served as substrates by beta-adrenoceptor kinase. The kinetics of the phosphorylation reaction, however, suggest that these peptides are 10(6)-fold poorer substrate than the agonist occupied receptor. 3. A number of synthetic peptides also served as inhibitors of beta 2-adrenoceptor phosphorylation by beta-adrenoceptor kinase. In particular, a peptide which comprised the first intracellular loop of the beta 2-adrenoceptor (amino acids 56-74) inhibited most effectively with an IC50 of 40 microM. 4. These results suggest that multiple intracellular regions of the beta-receptor may serve as potential sites of interaction with beta-adrenoceptor kinase. Moreover, these regions may serve as potential targets for the development of specific inhibitors of beta-adrenoceptor kinase which could be used to block homologous desensitization.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Benovic, J. L. and Onorato, J. and Lohse, M. J. and Dohlman, H. G. and Staniszewski, C. and Caron, M. G. and Lefkowitz, R. J.}, biburl = {https://www.bibsonomy.org/bibtex/26307f67bd8b6d837382583ac08525d4a/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {2ff36a9e47ab23ba0d1982e32cc97c69}, intrahash = {6307f67bd8b6d837382583ac08525d4a}, issn = {0306-5251 (Print) 0306-5251 (Linking)}, journal = {Br J Clin Pharmacol}, keywords = {AMP-Dependent Acid Amino Animals Cricetinae Cyclic Data Electrophoresis, GTP-Binding Gel Inhibitors Kinase Kinases Kinases/isolation Kinetics Molecular Peptides/chemical Phosphorylation Polyacrylamide Protein Proteins/metabolism Receptor Sequence Specificity Substrate beta-Adrenergic beta/*chemistry/metabolism purification/*metabolism synthesis/*metabolism/pharmacology Adrenergic}, note = {Benovic, J L Onorato, J Lohse, M J Dohlman, H G Staniszewski, C Caron, M G Lefkowitz, R J England British journal of clinical pharmacology Br J Clin Pharmacol. 1990;30 Suppl 1:3S-12S.}, pages = {3S-12S}, shorttitle = {Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase}, timestamp = {2010-12-14T18:22:38.000+0100}, title = {Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2176526}, volume = {30 Suppl 1}, year = 1990 }