Teaching old receptors new tricks: biasing seven-transmembrane receptors.
Seven-transmembrane receptors (7TMRs; also known as G protein-coupled receptors) are the largest class of receptors in the human genome and are common targets for therapeutics. Originally identified as mediators of 7TMR desensitization, beta-arrestins (arrestin 2 and arrestin 3) are now recognized as true adaptor proteins that transduce signals to multiple effector pathways. Signalling that is mediated by beta-arrestins has distinct biochemical and functional consequences from those mediated by G proteins, and several biased ligands and receptors have been identified that preferentially signal through either G protein- or beta-arrestin-mediated pathways. These ligands are not only useful tools for investigating the biochemistry of 7TMR signalling, they also have the potential to be developed into new classes of therapeutics.
Rajagopal
Sudarshan
S
Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina 27710, USA.
Rajagopal
Keshava
K
Lefkowitz
Robert J
RJ
D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D016503:Drug Delivery Systems; D015195:Drug Design; D015894:Genome, Human; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000071557:beta-Arrestins
D019390:Arrestins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; C082333:arrestin3; D000071557:beta-Arrestins; C450520:seven-transmembrane G-protein-coupled receptor