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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Perrin, M. H. Hjorth, S. A. Vale, W. W. Nielsen, S. M. Nielsen, L. Z. |
| Description | Author Affiliation: Nielsen SM ( The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Science, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.); |
| Abstract | Constitutive activity, or ligand-independent activity, of mutant G protein-coupled receptors (GPCRs) has been described extensively and implicated in the pathology of many diseases. Using the corticotropin-releasing factor (CRF) receptor and the thrombin receptor as a model, we present a ligand-dependent constitutive activation of a GPCR. A chimera in which the N-terminal domain of the CRF receptor is replaced by the amino-terminal 16 residues of CRF displays significant levels of constitutive activation. The activity, as measured by intracellular levels of cAMP, is blocked in a dose-dependent manner by the nonpeptide antagonist antalarmin. These results support a propinquity effect in CRF receptor activation, in which the amino-terminal portion of the CRF peptide is presented to the body of the receptor in the proper proximity for activation. This form of ligand-dependent constitutive activation may be of general applicability for the creation of constitutively activated GPCRs that are regulated by peptide ligands such as CRF. These chimeras may prove useful in analyzing mechanisms of receptor regulation and in the structural analysis of ligand activated receptors. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 18 |
| Volume Number | 97 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2000-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Receptors, Corticotropin-Releasing Hormone Physiology Receptors, Thrombin Amino Acid Sequence Animals COS Cells Corticotropin-Releasing Hormone Antagonists & Inhibitors Pharmacology Ligands Models, Molecular Molecular Sequence Data Peptide Fragments Chemistry Metabolism Protein Structure, Secondary Genetics Recombinant Fusion Proteins Transfection Urocortins Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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