p63RhoGEF: A New Switch for Gq-Mediated Activation of Smooth Muscle

In normal and diseased vascular smooth muscle (SM), the RhoA pathway, which is activated by multiple agonists through G protein–coupled receptors (GPCRs), plays a central role in regulating basal tone and peripheral resistance. Multiple RhoA GTP exchange factors (GEFs) are expressed in SM, raising the possibility that specific agonists coupled to specific GPCRs may couple to distinct RhoGEFs and provide novel therapeutic targets. This review focuses on the function and mechanisms of activation of p63RhoGEF (Arhgef 25; GEFT) recently identified in SM and its possible role in selective targeting of RhoA-mediated regulation of basal blood pressure through agonists that couple through Gαq/11.