Receptor activity-modifying partners (RAMPs) are a family of proteins that interact with G protein-coupled receptors (GPCRs) and alter GPCR activity. Prior experiments had demonstrated an interaction between RAMPs and the GPCRs calcitonin receptor and calcitonin receptor-like receptor, which alters their pharmacological profile. Christopoulos et al. show that, when RAMPs are cotransfected with GCPRs VPAC1, PTH1, PTH2, or the glucagon receptor, the RAMPs were expressed at higher levels at the cell surface, which suggests an interaction. The interactions appeared specific, that is, only RAMP2 increased at the cell surface when combined with PTH1, VPAC1, or glucagon receptors, and RAMP3 only increased at the surface when expressed with VPAC1 or PTH2. Investigation of the VPAC1-RAMP2 interaction showed that the maximum receptor binding sites and agonist potency were unchanged compared with VPAC1 expressed alone, which is different from the result of the calcitonin and calcitonin receptor-like receptor interaction with RAMPs. Instead, RAMP2 promoted coupling of VPAC1 to phosphoinositide turnover without changing VPAC1 stimulation of adenosine 3′,5′-monophosphate (cAMP) production. Thus, RAMPs appear to be pleiotropic GPCR regulators able to influence both receptor-ligand interactions and receptor-G protein interactions.
A. Christopoulos, G. Christopoulos, M. Morfis, M. Udawela, M. Laburthe, A. Couvineau, K. Kuwasako, N. Tilakaratne, P. M. Sexton, Novel receptor partners and function of receptor activity-modifying proteins. J. Biol. Chem. 278, 3293-3297 (2003). [Abstract] [Full Text]