Biased G Protein–Coupled Receptor Signaling

A direct and functional interaction between the trimeric G protein Go and Rab5 in G proteincoupled receptor signaling

Structure-Activity Investigation of a G Protein-Biased Agonist Reveals Molecular Determinants for Biased Signaling of the D2 Dopamine Receptor

The dopamine D2 receptor (D2R) is known to elicit effects through activating two major signaling pathways mediated by either G proteins (Gi/o) or β-arrestins. However, the specific role of each pathway in physiological or therapeutic activities is not known with certainty. One approach to the dissection of these pathways is through the use of drugs that can selectively modulate one pathway vs. ...

Agonist-biased signaling at the histamine H4 receptor: JNJ7777120 recruits β-arrestin without activating G proteins.

The G(i/o)-coupled histamine H(4) receptor is highly expressed in hemopoietic cells and is a promising new target for the treatment of chronic inflammatory diseases. 1-[(5-Chloro-1H-indol-2-yl)carbonyl]-4-methyl-piperazine (JNJ7777120) has been described as a selective antagonist at the H(4) receptor and is widely used to characterize the physiological role of the H(4) receptor. We have investi...

Allosteric and Biased G Protein-Coupled Receptor Signaling Regulation: Potentials for New Therapeutics

G protein-coupled receptors (GPCRs) are seven-transmembrane proteins that participate in many aspects of the endocrine function and are important targets for drug development. They transduce signals mainly, but not exclusively, via hetero-trimeric G proteins, leading to a diversity of intracellular signaling cascades. Ligands binding at the hormone orthosteric sites of receptors have been class...

Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy.

G protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters, representing the largest group of therapeutic targets. Recent studies show that some GPCRs signal through both G protein and arrestin pathways in a ligand-specific manner. Ligands that direct signaling through a specific pathway are known as biased ligands...