%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 }