The receptor activity-modifying protein (RAMP) family was first reported in 1998 during attempts to identify the cell surface receptor for a neuropeptide known as calcitonin gene-related peptide (CGRP) (McLatchie et al. 1998). Formerly, a protein known as the calcitonin receptor-like receptor (CLR) was thought to be the receptor for CGRP but no study had convincingly shown that this was the case. McLatchie and colleagues were able to show that CLR needs RAMP1 for a CGRP receptor to be formed. RAMP1 assists CLR in reaching the cell surface. Thus, RAMP1 and CLR together at the cell surface form the receptor for CGRP, which binds and activates this protein complex, leading to downstream signaling events such as an accumulation of intracellular cAMP. In this same study, two other related proteins were found, named RAMP2 and RAMP3. Each of these proteins could also assist CLR in reaching the cell surface but remarkably, CGRP was less effective at activating these...
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