Modulating receptor function through RAMPs: can they represent drug targets in themselves?
G protein-coupled receptors (GPCRs) are successfully exploited as drug targets. As our understanding of how distinct GPCR subtypes can be generated expands, so do possibilities for therapeutic intervention via these receptors. Receptor activity-modifying proteins (RAMPs) are excellent examples of proteins that enhance diversity in GPCR function. They facilitate the creation of binding pockets, controlling the pharmacology of some GPCRs. Moreover, they have the ability to regulate cell-surface trafficking, internalisation and signalling of GPCRs, creating novel opportunities for drug discovery. RAMPs could be directly targeted by drugs, or advantage could be taken of unique RAMP/GPCR interfaces for generating highly selective ligands.
Sexton
Patrick M
PM
Drug Discovery Biology Laboratory, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Victoria 3800, Australia.
Poyner
David R
DR
Simms
John
J
Christopoulos
Arthur
A
Hay
Debbie L
DL
D000818:Animals; D001665:Binding Sites; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D015394:Molecular Structure; D011485:Protein Binding; D021381:Protein Transport; D058261:Receptor Activity-Modifying Proteins; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D058261:Receptor Activity-Modifying Proteins; D043562:Receptors, G-Protein-Coupled