LARG links histamine-H1-receptor-activated Gq to Rho-GTPase-dependent signaling pathways

► Specific coupling of HRH1 to Gq is used to analyze the role of Gαq in LARG activation. ► HRH1-mediated LARG activation requires the LARG PDZ domain. ► Gαq-mediated activation of LARG is independent of PLCβ activation. ► Gαq-mediated activation of LARG requires no more than the LARG DH-PH tandem. ► Mechanisms of Gαq-mediated activation of LARG, p63RhoGEF, and PLCβ3 are distinct.