G protein-coupled receptors (GPCRs) constitute a family of membrane proteins that transduce exterior stimuli into intracellular signals. GPCRs are also known as seven-transmembrane domain receptors, heptahelical receptors, serpentine receptors, or G protein-linked receptors (Lefkowitz, 2000).
In the 1970s and early 1980s, major biochemical and pharmacological GPCR studies were coincidently conducted for the apparently unrelated visual and hormonal signaling pathways of rhodopsin and β2 adrenergic receptor (β2AR). With the advent of molecular biological techniques, massive numbers of nucleotide sequences coding for these proteins were determined. The decade beginning in the mid-1980s was a golden age for gene cloning; a number of membrane receptors were also cloned (Nathans and Hogness, 1983; Dixon
β2AR was originally recognized as a regulatory component that controls the activity of adenylyl cyclase (Robison
Recent progress in the crystallographic structure determination of GPCRs (Cherezov
Along with molecular and structural biological research, studies with knockout animals or ones with hypomorphic mutations are increasingly impactful. In connection with completed human genome projects, a genomic approach will be important to understand the link between GPCR polymorphism and heterogeneity of drug efficacy in the population.
This special issue of
In response to agonist stimulation, GPCRs couple to the GDP-bound form of G proteins, and GDP on the Gα subunit is replaced by GTP, which induces dissociation of the Gα subunit from the GPCR and Gβγ subunits. In the first review, “Recent progress in understanding the conformational mechanism of heterotrimeric G protein activation,” Duc
As their names imply, arrestins have been chiefly considered to be mediators that induce GPCR desensitization via steric hindrance. However, over the last decade, β-arrestins are increasingly being recognized as mediators of G proteinindependent signaling (Reiter
Along with signaling through G proteins, agonist-induced conformational changes in the intracellular domains promote the association of the receptor with G protein-coupled receptor kinases (GRKs) (Zheng
The phenomenon in which the signaling of a given receptor is regulated by a different class of receptor is designated as transactivation or crosstalk. Receptor tyrosine kinases (RTKs) and GPCRs are two major membrane receptor groups that employ distinct signal transduction systems. It has long been known that agonists of some GPCRs can activate RTKs in the absence of growth factor stimulation (van Biesen
High-throughput screening is an experimental approach employed in modern drug discovery. This technique has the advantage of rapid and efficient handling of a large number of samples (Agresti
Viruses use diverse approaches to take advantage of host cells for successful replication and continued pathogenesis. Hijacking host GPCRs into the viral genome is a tactic commonly deployed by viruses (Sodhi
GPCRs represent a major drug target in all clinical areas. According to the fifth review (Furlong and Seong, 2017) and the seventh review (Park and Im, 2017), GPCRs are the largest membrane-bound receptor superfamily in humans, with over 840 members. Because of the variety and selectivity of GPCRs, approximately 30–40% of current prescription drugs target them. In the last review of this issue, “Sphingosine-1-phosphate receptor modulators and drug discovery,” Park and Im (2017) discuss the status of drugs targeting sphingosine-1-phosphate receptors, with a focus on potential clinical applications.
This work was funded by KRF- 2014R1A2A2A01002547.