title: Receptor-activity-modifying protein 1 forms heterodimers with two G-protein-coupled receptors to define ligand recognition.
abstract: Receptor-activity-modifying proteins (RAMPs) with single transmembrane domains define the function of two G-protein-coupled receptors of the B family. Cell-surface complexes of human RAMP1 (hRAMP1) and human calcitonin (CT) receptor isotype 2 (hCTR2) or rat CT-receptor-like receptor (rCRLR) have now been identified through protein cross-linking, co-immunoprecipitation and confocal microscopy. They are two distinct CT-gene-related peptide (CGRP) receptors coupled to cAMP production and pharmacologically distinguished by the CT and CGRP antagonists salmon CT(8-32) and human or rat CGRP(8-37). Thus direct molecular interactions of hRAMP1 with hCTR2 or rCRLR are required for CGRP recognition. hCTR2, moreover, adopts non-traditional functions through its association with hRAMP1.
authors.affiliation: Research Laboratory for Calcium Metabolism, Departments of Orthopaedic Surgery and Medicine, University of Zurich, Klinik Balgrist, Forchstr. 340, CH-8008 Zurich, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Leuthäuser
authors.forename: R
authors.initials: R
authors.lastname: Gujer
authors.forename: A
authors.initials: A
authors.lastname: Aldecoa
authors.forename: R A
authors.initials: RA
authors.lastname: McKinney
authors.forename: R
authors.initials: R
authors.lastname: Muff
authors.forename: J A
authors.initials: JA
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: Born
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D014162:Transfection
chemical_list: D003432:Cross-Linking Reagents; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; C545502:RAMP1 protein, human; C545508:Ramp1 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; D000242:Cyclic AMP; D019204:GTP-Binding Proteins