Source:http://linkedlifedata.com/resource/pubmed/id/10385705
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1999-7-22
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pubmed:abstractText |
Receptor activity-modifying proteins (RAMPs) are single-transmembrane proteins that transport the calcitonin receptor-like receptor (CRLR) to the cell surface. RAMP 1-transported CRLR is a calcitonin gene-related peptide (CGRP) receptor. RAMP 2- or RAMP 3-transported CRLR is an adrenomedullin receptor. The role of RAMPs beyond their interaction with CRLR, a class II G protein-coupled receptor, is unclear. In this study, we have examined the role of RAMPs in generating amylin receptor phenotypes from the calcitonin (CT) receptor gene product. Cotransfection of RAMP 1 or RAMP 3 with the human CT receptor lacking the 16-amino acid insert in intracellular domain 1 (hCTRI1-) into COS-7 cells induced specific 125I-labeled rat amylin binding. RAMP 2 or vector cotransfection did not cause significant increases in specific amylin binding. Competition-binding characterization of the RAMP-induced amylin receptors revealed two distinct phenotypes. The RAMP 1-derived amylin receptor demonstrated the highest affinity for salmon CT (IC50, 3.01 +/- 1.44 x 10(-10) M), a high to moderate affinity for rat amylin (IC50, 7.86 +/- 4.49 x 10(-9) M) and human CGRPalpha (IC50, 2.09 +/- 1.63 x 10(-8) M), and a low affinity for human CT (IC50, 4.47 +/- 0.78 x 10(-7) M). In contrast, whereas affinities for amylin and the CTs were similar for the RAMP 3-derived receptor, the efficacy of human CGRPalpha was markedly reduced (IC50, 1.12 +/- 0.45 x 10(-7) M; P <.05 versus RAMP 1). Functional cyclic AMP responses in COS-7 cells cotransfected with individual RAMPs and hCTRI1- were reflective of the phenotypes seen in competition for amylin binding. Confocal microscopic localization of c-myc-tagged RAMP 1 indicated that, when transfected alone, RAMP 1 almost exclusively was located intracellularly. Cotransfection with calcitonin receptor (CTR)I1- induced cell surface expression of RAMP 1. The results of experiments cross-linking 125I-labeled amylin to RAMP 1/hCTR-transfected cells with bis succidimidyl suberate were suggestive of a cell-surface association of RAMP 1 and the receptors. Our data suggest that in the CT family of receptors, and potentially in other class II G protein-coupled receptors, the cellular phenotype is likely to be dynamic in regard to the level and combination of both the receptor and the RAMP proteins.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activity-Modifying Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitonin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Islet Amyloid Polypeptide,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Peptide
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
235-42
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10385705-Animals,
pubmed-meshheading:10385705-Binding, Competitive,
pubmed-meshheading:10385705-CHO Cells,
pubmed-meshheading:10385705-COS Cells,
pubmed-meshheading:10385705-Cells, Cultured,
pubmed-meshheading:10385705-Cercopithecus aethiops,
pubmed-meshheading:10385705-Cricetinae,
pubmed-meshheading:10385705-Cyclic AMP,
pubmed-meshheading:10385705-Dose-Response Relationship, Drug,
pubmed-meshheading:10385705-Humans,
pubmed-meshheading:10385705-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10385705-Membrane Proteins,
pubmed-meshheading:10385705-Receptor Activity-Modifying Proteins,
pubmed-meshheading:10385705-Receptors, Calcitonin,
pubmed-meshheading:10385705-Receptors, Islet Amyloid Polypeptide,
pubmed-meshheading:10385705-Receptors, Peptide
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pubmed:year |
1999
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pubmed:articleTitle |
Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product.
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pubmed:affiliation |
Molecular Pharmacology Laboratory, Department of Pharmacology, The University of Melbourne, Victoria, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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