title: Ultrasensitivity part II: multisite phosphorylation, stoichiometric inhibitors, and positive feedback.
abstract: In this series of reviews, we are examining ultrasensitive responses, the switch-like input-output relationships that contribute to signal processing in a wide variety of signaling contexts. In the first part of this series, we explored one mechanism for generating ultrasensitivity, zero-order ultrasensitivity, where the saturation of two converting enzymes allows the output to switch from low to high over a tight range of input levels. In this second installment, we focus on three conceptually distinct mechanisms for ultrasensitivity: multisite phosphorylation, stoichiometric inhibitors, and positive feedback. We also examine several related mechanisms and concepts, including cooperativity, reciprocal regulation, coherent feed-forward regulation, and substrate competition, and provide several examples of signaling processes where these mechanisms are known or are suspected to be applicable.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford CA 94305-5174, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Ferrell
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford CA 94305-5174, USA.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ha
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D025461:Feedback, Physiological; D006801:Humans; D007700:Kinetics; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases