CXCR3, with VUF10661 and CXCL11 being the most efficacious ligands. We also observed that GRK3 and GRK5 are able to traffic to endosomes following ligand stimulation with VUF10661 even though all ligands are able to promote receptor internalization. Given biased engagement of the GRKs observed at both the receptor and in endosomes, we next studied the functional consequences of ligand and location bias by creating GRK 2, 3, 5 and 6 constructs that are specifically targeted to the plasma membrane or the endosome. Using GRK2/3/5/6 KO cells, we determined that localization of the GRKs impacts receptor internalization, ERK activity, and transcription in a ligand specific manner. We observed that the endogenous and synthetic ligands of CXCR3 demonstrate biased engagement of the GRKs at different subcellular locations and highlight the functional significance of these findings on downstream receptor signaling. Together, these data provide evidence that the functional selectivity of biased signaling extends beyond β-arrestins and G-proteins to other effector proteins that interact with GPCRs. 33 | P a g e
- Subject
- VUF
- Type
- course
- Edition
- 2026
- Source
- undergraduateresearch.duke.edu