Membrane signaling proteins transduce information across lipid bilayer membranes in response to extra-cellular binding of chemical messengers. The design of chemical systems that initiate transmembrane signal transduction through molecular binding events is a critical step toward preparing responsive synthetic vesicles. Here we report a vesicle-based signaling system controlled by a metal cation binding event. Competition between binding of copper ions to a membrane-embedded synthetic transducer and to an extra-vesicle messenger (EDTA) is used to control translocation of the transducer across the lipid bilayer. The translocation process is coupled to activation of a catalyst that turns over encapsulated substrates on the inside of the vesicle to generate an amplified fluorescence output signal. External EDTA and copper ions can be used to reversibly switch catalysis inside the vesicles on and off in a controlled manner.