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PMID: 9620797 Published · ppublish English Journal Article

RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.

Nature ·Vol. 393 ·No. 6683 ·1998-05-28 ·Pages 333-9

McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM

Abstract

Calcitonin-gene-related peptide (CGRP) and adrenomedullin are related peptides with distinct pharmacological profiles. Here we show that a receptor with seven transmembrane domains, the calcitonin-receptor-like receptor (CRLR), can function as either a CGRP receptor or an adrenomedullin receptor, depending on which members of a new family of single-transmembrane-domain proteins, which we have called receptor-activity-modifying proteins or RAMPs, are expressed. RAMPs are required to transport CRLR to the plasma membrane. RAMP1 presents the receptor at the cell surface as a mature glycoprotein and a CGRP receptor. RAMP2-transported receptors are core-glycosylated and are adrenomedullin receptors.

MeSH Terms
3T3 Cells Adrenomedullin Amino Acid Sequence Animals Biological Transport Calcitonin/chemistry,metabolism Calcitonin Gene-Related Peptide/genetics,metabolism Calcitonin Receptor-Like Protein Cell Line Cloning, Molecular Cross-Linking Reagents Cystic Fibrosis Transmembrane Conductance Regulator/metabolism Gene Expression Glycosylation Humans Intracellular Signaling Peptides and Proteins Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase/metabolism Membrane Proteins/genetics,metabolism Mice Molecular Sequence Data Peptides/metabolism RNA, Messenger/metabolism Receptor Activity-Modifying Protein 1 Receptor Activity-Modifying Protein 2 Receptor Activity-Modifying Proteins Receptors, Adrenomedullin Receptors, Calcitonin/metabolism Receptors, Calcitonin Gene-Related Peptide/genetics,metabolism Receptors, Peptide Sequence Alignment Tumor Cells, Cultured Xenopus
Chemicals
CALCRL protein, human CFTR protein, human Calcitonin Receptor-Like Protein Calcrl protein, mouse Cross-Linking Reagents Intracellular Signaling Peptides and Proteins Membrane Proteins Peptides RAMP1 protein, human RAMP2 protein, human RNA, Messenger Ramp1 protein, mouse Ramp2 protein, mouse Receptor Activity-Modifying Protein 1 Receptor Activity-Modifying Protein 2 Receptor Activity-Modifying Proteins Receptors, Adrenomedullin Receptors, Calcitonin Receptors, Calcitonin Gene-Related Peptide Receptors, Peptide Cystic Fibrosis Transmembrane Conductance Regulator Adrenomedullin Calcitonin Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase Calcitonin Gene-Related Peptide
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
McLatchie L M
Receptor Systems and Cell Biology Units, Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire, UK.
Fraser N J
Main M J
Wise A
Brown J
Thompson N
Solari R
Lee M G
Foord S M
Article Info
Journal
Nature
Abbr.
Nature
ISSN
0028-0836
Published
1998-05-28
Pages
333-9
Language
English
Region
England
NLM ID
0410462
Subset
IM
Databases
GENBANK
AJ001014, AJ001015, AJ001016
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