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17 Nov 2021

RAMP’s: G-Protein coupled receptor accessory proteins with vital biological roles

Receptor activity-modifying proteins (RAMPs) are a family of single-transmembrane receptor accessory proteins which include RAMP-1, RAMP-2 and RAMP-3 that are involved in several cellular pathways of high importance. Here at Discovery Antibodies® we offer high-quality specific antibodies to each of the three RAMP proteins which are able to detect their target proteins in Western blot and immuno-histochemical applications. RAMPs act by binding to G-protein coupled receptors (GPCRs), which are vital in intercellular signalling, and alter their pharmacology such as changing ligand specificity and mediating receptor trafficking. RAMPs play essential roles in several body systems and mutations in RAMP-GPCR pairings have been identified and linked to human disease. Therefore this interesting protein family is of high value for studying and understanding many human disease pathways.

RAMPs interact with class B GPCRs and several GPCRs from other families, including: calcitonin receptor (CTR) and calcitonin-like receptor (CLR), the vasoactive intestinal polypeptide/pituitary AC-activating peptide 1 (VPAC1) receptor, glucagon receptor (GCGR), corticotropin-releasing factor receptors (CRF) parathyroid hormone receptors, secretin receptor, and pituitary adenylate cyclase activating peptide (PACAP) receptors.

Perhaps the most well studied role for RAMPs is their binding to and regulation of CTR and CLR. RAMPs are able to modulate several aspects of receptor function including receptor trafficking to the cell surface, recycling, ligand binding preference, signal transduction, post-translational modifications, and G-protein coupling. The peptide ligands that bind to CTR and CLR: include calcitonin (CT), amylin, calcitonin gene-related peptides α and β (αCGRP and βCGRP), adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2/IMD), many of which are available in our Discovery Peptides catalogue.

References:

Hay and Pioszak (2015). RAMPs (Receptor-Activity Modifying Proteins): New Insights and Roles. Annu. Rev. Pharmacol. Toxicol. 56: 469 PMID: 26514202

McLatchie et al., (1998). RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature. 393(6683): 333. PMID: 9620797

Suekane et al., (2019). CGRP-CRLR/RAMP1 signal is important for stress-induced hematopoiesis. Sci Rep. 9(1). PMID: 30674976