Engineered anthrax protective antigen (PrAg) proteins are provided wherein the native furin activation site is replaced by the activation site of a membrane-anchored serine protease. These engineered PrAg proteins retain the ability to bind to cell surface PrAg receptors and be proteolytically activated. The proteins also retain the ability to form membrane pores. These engineered PrAg proteins can be used in methods of inducing pore formation in a cell, methods of inducing translocation of a selected compound or co-factor into a cell, and methods of treating disease, such as cancer, in a subject.
