The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
CGRP-RCP, a Novel Protein Required for Signal Transduction at Calcitonin Gene-related Peptide and Adrenomedullin Receptors
Open accessAbstract
It is becoming clear that receptors that initiate signal transduction by interacting with G-proteins do not function as monomers, but often require accessory proteins for function. Some of these accessory proteins are chaperones, required for correct transport of the receptor to the cell surface, but the function of many accessory proteins remains unknown. We determined the role of an accessory protein for the receptor for calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide. We have previously shown that this accessory protein, the CGRP-receptor component protein (RCP), is expressed in CGRP responsive tissues and that RCP protein expression correlates with the biological efficacy of CGRP in vivo. However, the function of RCP has remained elusive. In this study stable cell lines were made that express antisense RCP RNA, and CGRP- and adrenomedullin-mediated signal transduction were greatly reduced. However, the loss of RCP did not effect CGRP binding or receptor density, indicating that RCP did not behave as a chaperone but was instead coupling the CGRP receptor to downstream effectors. A candidate CGRP receptor named calcitonin receptor-like receptor (CRLR) has been identified, and in this study RCP co-immunoprecipitated with CRLR indicating that these two proteins interact directly. Since CGRP and adrenomedullin can both signal through CRLR, which has been previously shown to require a chaperone protein for function, we now propose that a functional CGRP or adrenomedullin receptor consists of at least three proteins: the receptor (CRLR), the chaperone protein (RAMP), and RCP that couples the receptor to the cellular signal transduction pathway.
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Cites
RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor
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A cDNA Encoding the Calcitonin Gene-related Peptide Type 1 Receptor
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Cited by
Calcitonin Gene-Related Peptide: Physiology and Pathophysiology
Russell, F. A., King, R., Smillie, S.-J., Kodji, X., & Brain, S. D. (2014) · Physiological Reviews · doi:10.1152/physrev.00034.2013 · Cited by 1,258
Models and Mechanisms of Hyperalgesia and Allodynia
Sandkühler, J. (2009) · Physiological Reviews · doi:10.1152/physrev.00025.2008 · Cited by 1,148
G Protein-Coupled Receptor Allosterism and Complexing
Christopoulos, A., & Kenakin, T. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.323 · Cited by 931
Poyner, D. R., Sexton, P. M., Marshall, I., Smith, D. M., Quirion, R., Born, W., Muff, R., Fischer, J. A., & Foord, S. M. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.233 · Cited by 804
Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin
Brain, S. D., & Grant, A. D. (2004) · Physiological Reviews · doi:10.1152/physrev.00037.2003 · Cited by 765
Metadata
- Authors
- Evans, B. N., Rosenblatt, M. I., Mnayer, L. O., Oliver, K. R., & Dickerson, I. M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 275
- Issue
- 40
- Pages
- 31438-31443
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2084093310
- Cited by
- 337
- References
- 25
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
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