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. 2000 Oct 15;351(Pt 2):347–351.

Receptor-activity-modifying protein 1 forms heterodimers with two G-protein-coupled receptors to define ligand recognition.

K Leuthäuser 1, R Gujer 1, A Aldecoa 1, R A McKinney 1, R Muff 1, J A Fischer 1, W Born 1
PMCID: PMC1221370  PMID: 11023820

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bühlmann N., Leuthäuser K., Muff R., Fischer J. A., Born W. A receptor activity modifying protein (RAMP)2-dependent adrenomedullin receptor is a calcitonin gene-related peptide receptor when coexpressed with human RAMP1. Endocrinology. 1999 Jun;140(6):2883–2890. doi: 10.1210/endo.140.6.6783. [DOI] [PubMed] [Google Scholar]
  2. Chang C. P., Pearse R. V., 2nd, O'Connell S., Rosenfeld M. G. Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain. Neuron. 1993 Dec;11(6):1187–1195. doi: 10.1016/0896-6273(93)90230-o. [DOI] [PubMed] [Google Scholar]
  3. Christopoulos G., Perry K. J., Morfis M., Tilakaratne N., Gao Y., Fraser N. J., Main M. J., Foord S. M., Sexton P. M. Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol. 1999 Jul;56(1):235–242. doi: 10.1124/mol.56.1.235. [DOI] [PubMed] [Google Scholar]
  4. Dennis T., Fournier A., Cadieux A., Pomerleau F., Jolicoeur F. B., St Pierre S., Quirion R. hCGRP8-37, a calcitonin gene-related peptide antagonist revealing calcitonin gene-related peptide receptor heterogeneity in brain and periphery. J Pharmacol Exp Ther. 1990 Jul;254(1):123–128. [PubMed] [Google Scholar]
  5. Flühmann B., Lauber M., Lichtensteiger W., Fischer J. A., Born W. Tissue-specific mRNA expression of a calcitonin receptor-like receptor during fetal and postnatal development. Brain Res. 1997 Nov 7;774(1-2):184–192. doi: 10.1016/s0006-8993(97)81702-7. [DOI] [PubMed] [Google Scholar]
  6. Flühmann B., Muff R., Hunziker W., Fischer J. A., Born W. A human orphan calcitonin receptor-like structure. Biochem Biophys Res Commun. 1995 Jan 5;206(1):341–347. doi: 10.1006/bbrc.1995.1047. [DOI] [PubMed] [Google Scholar]
  7. Fraser N. J., Wise A., Brown J., McLatchie L. M., Main M. J., Foord S. M. The amino terminus of receptor activity modifying proteins is a critical determinant of glycosylation state and ligand binding of calcitonin receptor-like receptor. Mol Pharmacol. 1999 Jun;55(6):1054–1059. doi: 10.1124/mol.55.6.1054. [DOI] [PubMed] [Google Scholar]
  8. Henke H., Tschopp F. A., Fischer J. A. Distinct binding sites for calcitonin gene-related peptide and salmon calcitonin in rat central nervous system. Brain Res. 1985 Dec 23;360(1-2):165–171. doi: 10.1016/0006-8993(85)91232-6. [DOI] [PubMed] [Google Scholar]
  9. Husmann K., Sexton P. M., Fischer J. A., Born W. Mouse receptor-activity-modifying proteins 1, -2 and -3: amino acid sequence, expression and function. Mol Cell Endocrinol. 2000 Apr 25;162(1-2):35–43. doi: 10.1016/s0303-7207(00)00212-4. [DOI] [PubMed] [Google Scholar]
  10. Kuestner R. E., Elrod R. D., Grant F. J., Hagen F. S., Kuijper J. L., Matthewes S. L., O'Hara P. J., Sheppard P. O., Stroop S. D., Thompson D. L. Cloning and characterization of an abundant subtype of the human calcitonin receptor. Mol Pharmacol. 1994 Aug;46(2):246–255. [PubMed] [Google Scholar]
  11. McLatchie L. M., Fraser N. J., Main M. J., Wise A., Brown J., Thompson N., Solari R., Lee M. G., Foord S. M. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature. 1998 May 28;393(6683):333–339. doi: 10.1038/30666. [DOI] [PubMed] [Google Scholar]
  12. Muff R., Bühlmann N., Fischer J. A., Born W. An amylin receptor is revealed following co-transfection of a calcitonin receptor with receptor activity modifying proteins-1 or -3. Endocrinology. 1999 Jun;140(6):2924–2927. doi: 10.1210/endo.140.6.6930. [DOI] [PubMed] [Google Scholar]
  13. Sexton P. M., Findlay D. M., Martin T. J. Calcitonin. Curr Med Chem. 1999 Nov;6(11):1067–1093. [PubMed] [Google Scholar]
  14. Sexton P. M., Houssami S., Hilton J. M., O'Keeffe L. M., Center R. J., Gillespie M. T., Darcy P., Findlay D. M. Identification of brain isoforms of the rat calcitonin receptor. Mol Endocrinol. 1993 Jun;7(6):815–821. doi: 10.1210/mend.7.6.8395656. [DOI] [PubMed] [Google Scholar]
  15. Wimalawansa S. J. Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr Rev. 1996 Oct;17(5):533–585. doi: 10.1210/edrv-17-5-533. [DOI] [PubMed] [Google Scholar]
  16. Zimmermann U., Fluehmann B., Born W., Fischer J. A., Muff R. Coexistence of novel amylin-binding sites with calcitonin receptors in human breast carcinoma MCF-7 cells. J Endocrinol. 1997 Dec;155(3):423–431. doi: 10.1677/joe.0.1550423. [DOI] [PubMed] [Google Scholar]

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