CPM enhances B1R signaling independent of its enzyme activity and substrate specificity. The dose-dependent increase in [Ca2+]i stimulated by DAKD was measured in HEK cells stably expressing B1R alone or B1R with CPM-E264Q, a mutant that lacks enzyme activity (A), CPM S180N, an active mutant that reverses the preference of CPM for cleaving C-terminal Arg to Lys (B), and CPM S180N E264Q, a mutant with Lys specificity for substrate binding, but without enzyme activity (C). The data shown are representative examples from three experiments.