title: The role of proofreading in signal transduction specificity.
abstract: Many intracellular signaling proteins such as MAP kinases and transcription factors require multiple covalent modifications before activating downstream targets. This property suggests that signaling pathways are organized to facilitate proofreading, which expends energy to enhance the specificity of the pathway for the appropriate effector. Focusing on MAP kinases, we show that each phosphorylation of the kinase can act as an independent specificity test for that kinase. This is independent of whether MAP kinase activation is distributive, processive, or confined to a protein scaffold. We also highlight the importance of phosphatases in developing and maintaining specificity. Support for our proposals can be drawn from the existing literature.
authors.affiliation: Center for Studies in Physics and Biology, The Rockefeller University, New York, New York 10021, USA. swain@papagena.rockefeller.edu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Swain
authors.forename: Eric D
authors.initials: ED
authors.lastname: Siggia
mesh_terms: D055592:Biophysical Phenomena; D001703:Biophysics; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases