Ultrasensitivity part III: cascades, bistable switches, and oscillators

Switch-like, ultrasensitive responses - responses that resemble those of cooperative enzymes but are not necessarily generated by cooperativity - are widespread in signal transduction. In the previous installments in this series, we reviewed several mechanisms for generating ultrasensitivity: zero-order ultrasensitivity; multistep ultrasensitivity; inhibitor ultrasensitivity; and positive feedback (or double negative feedback) loops. In this review, we focus on how ultrasensitive components can be important for the functioning of more complex signaling circuits. Ultrasensitivity can allow the effective transmission of signals down a signaling cascade, can contribute to the generation of bistability by positive feedback, and can promote the production of biochemical oscillations in negative feedback loops. This makes ultrasensitivity a key building block in systems biology and synthetic biology.