PARtitioning protease signaling

摘要

In this issue of Blood, Aisiku et al describe a novel class of protease-activated receptor-1 (PAR1) inhibitors that block proinflammatory pathways but spare cytoprotective signaling in endothelial cells.(1) These compounds, parmodulins, target the cytoplasmic face of PAR1, where they selectively interfere with G alpha(q), but not G alpha(12/13). This strategy of blocking specific pathways provides the ability to modulate the activity of receptors with multiple functions (such as PAR1) and may have therapeutic advantages.