The role of proofreading in signal transduction specificity

Peter S Swain, Eric D Siggia

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)2928-33
Number of pages6
JournalBiophysical Journal
Issue number6
Publication statusPublished - 2002


  • Biophysical Phenomena
  • Biophysics
  • Enzyme Activation
  • Humans
  • Kinetics
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases
  • Models, Biological
  • Phosphorylation
  • Saccharomyces cerevisiae
  • Signal Transduction


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