Abstract: Modular synthetic receptors are provided. The synthetic receptors may include an extracellular domain capable of binding to one or more ligand molecules and may be released from the synthetic receptor after binding, a transmembrane domain derived from the Notch receptor, and an intracellular domain which may have one or more functional activities when released from the synthetic receptor. A method of use for the synthetic receptors is also provided, wherein upon binding of the extracellular domain to a specific ligand, the synthetic receptor undergoes proteolytic cleavage to release either or both the extracellular and intracellular domains. The extracellular binding domain, if released, may continue to bind to its cognate ligand and may carry one or more additional functional activities and the intracellular domain, if released, may stimulate or inhibit one or more intracellular activities.