Rewiring MAP Kinase Pathways Using Alternative Scaffold Assembly Mechanisms

  • Sang-Hyun Park
    Department of Cellular and Molecular Pharmacology and Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
  • Ali Zarrinpar
    Department of Cellular and Molecular Pharmacology and Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
  • Wendell A. Lim
    Department of Cellular and Molecular Pharmacology and Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

書誌事項

公開日
2003-02-14
DOI
  • 10.1126/science.1076979
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:p>How scaffold proteins control information flow in signaling pathways is poorly understood: Do they simply tether components, or do they precisely orient and activate them? We found that the yeast mitogen-activated protein (MAP) kinase scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous protein interactions could functionally replace native kinase recruitment interactions, indicating that simple tethering is largely sufficient for scaffold-mediated signaling. Moreover, by engineering a scaffold that tethers a unique kinase set, we could create a synthetic MAP kinase pathway with non-natural input-output properties. These findings demonstrate that scaffolds are highly flexible organizing factors that can facilitate pathway evolution and engineering.</jats:p>

収録刊行物

  • Science

    Science 299 (5609), 1061-1064, 2003-02-14

    American Association for the Advancement of Science (AAAS)

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