Controlling the G-protein signaling of Rs1

Constitutive signaling and ligand-induced signaling of Rs1 were successfully controlled by point mutations, drug choice, and domain swapping. Gq signaling of Rs1 could be activated by zacopride or RS23597 but not GR113808, GR125487 or RO110-0235. The signaling was significantly increased by switching the carboxyl tail (Rs1.1). Attempts to decrease constitutive activity also decreased ligand-induced Gs signaling and abolished Gq signaling (Rs1.2). Replacing i3 of Rs1 with that of 5-HT1A resulted in a Gi coupled RASSL with no Gs/q signaling and Gi signaling (Rs1.3).