Signaling bias of the protease-activated receptor-1 is dictated by distinct GRK5 and β-arrestin-2 determinants - PubMed
3 days ago
- #PAR1
- #signaling bias
- #GPCR
- GPCRs exhibit signaling bias, preferring G proteins or GRK-mediated β-arrestin signaling.
- PAR1 activates G protein and β-arrestin with thrombin but only β-arrestin with APC.
- Thrombin-activated PAR1-G protein signaling is desensitized by β-arrestin-1; APC-activated PAR1 signaling is propagated by β-arrestin-2.
- Mechanisms of PAR1 biased signaling involve GRK5 regulation, membrane anchoring, and β-arrestin-2 binding modes.
- Distinct β-arrestin-2 conformations define APC cytoprotective signaling versus thrombin inflammatory signaling.