Subcellular localization of GPCR kinases differentially modulate biased signaling at CXCR3
Gardner, J.; Eiger, D. S.; Hicks, C.; Choi, I.; Pham, U.; Rajagopal, S.
Show abstract
Some G protein-coupled receptors (GPCRs) demonstrate biased signaling, where ligands of the same receptor differentially activate specific downstream signaling pathways over others. Ligand-specific receptor phosphorylation by GPCR kinases (GRKs) is one mechanism underlying this phenomenon. Recent evidence demonstrates that GPCRs traffic to and signal from subcellular compartments beyond the plasma membrane, a paradigm termed location bias. Here, we show that GRKs translocate to endosomes following stimulation of the chemokine receptor CXCR3 and other GPCRs. The GRK recruitment patterns at the plasma membrane and endosome are distinct and depend on the identity of the ligand used to activate the receptor. Using cells deficient of GRKs, we demonstrate that biased ligands have unique signaling profiles upon rescue of location-specific GRK isoforms. Our work highlights a role of the GRKs in location-biased GPCR signaling and demonstrates the complex interactions between ligand, GRK isoform and cellular location that contribute to biased signaling.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Rules of engagement: determinants of chemokine receptor activation and selectivity by CCL27 and CCL28 94%
- Multiple mechanisms of self-association of chemokine receptors CXCR4 and CCR5 demonstrated by deep mutagenesis 93%
- Angiotensin receptor conformations stabilized by biased ligands differentially modulate β-arrestin interactions 93%
Similar papers in this journal
- Atypical Chemokine Receptor 3 'Senses' CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation 97%
- Inhibition of constitutive activity of the atypical chemokine receptor ACKR3 by the small-molecule inverse agonist VUF16840 95%
- CXCR1 and CXCR2 display receptor bias for shared chemokine agonists 95%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.