Complexing receptor pharmacology: modulation of family B G protein-coupled receptor function by RAMPs.
The most well-characterized subgroup of family B G protein-coupledreceptors (GPCRs) comprises receptors for peptide hormones, such as secretin, calcitonin (CT), glucagon, and vasoactive intestinal peptide (VIP). Recent data suggest that many of these receptors can interact with a novel family of GPCR accessory proteins termed receptor activity modifying proteins (RAMPs). RAMP interaction with receptors can lead to a variety of actions that include chaperoning of the receptor protein to the cell surface as is the case for the calcitonin receptor-like receptor (CLR) and the generation of novel receptor phenotypes. RAMP heterodimerization with the CLR and related CT receptor is required for the formation of specific CT gene-related peptide, adrenomedullin (AM) or amylin receptors. More recent work has revealed that the specific RAMP present in a heterodimer may modulate other functions such as receptor internalization and recycling and also the strength of activation of downstream signaling pathways. In this article we review our current state of knowledge of the consequence of RAMP interaction with family B GPCRs.
Sexton
Patrick M
PM
Howard Florey Institute, Level 2, Alan Gilbert Building, The University of Melbourne, 161 Barry Street, Carlton South, 3053, Victoria, Australia. p.sexton@hfi.unimelb.edu.au
Morfis
Maria
M
Tilakaratne
Nanda
N
Hay
Debbie L
DL
Udawela
Madhara
M
Christopoulos
George
G
Christopoulos
Arthur
A
D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D058261:Receptor Activity-Modifying Proteins; D043562:Receptors, G-Protein-Coupled / Q000145:classification* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D058261:Receptor Activity-Modifying Proteins; D043562:Receptors, G-Protein-Coupled