1. Biochemistry and Chemical Biology
  2. Cell Biology
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Unfair competition governs the interaction of pCPI-17 with myosin phosphatase (PP1-MYPT1)

  1. Joshua J Filter
  2. Byron C Williams
  3. Masumi Eto
  4. David Shalloway
  5. Michael L Goldberg  Is a corresponding author
  1. Cornell University, United States
  2. Sidney Kimmel Medical College at Thomas Jefferson University, United States
Research Article
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Cite this article as: eLife 2017;6:e24665 doi: 10.7554/eLife.24665

Abstract

The small phosphoprotein pCPI-17 inhibits myosin light chain phosphatase (MLCP). Current models postulate that during muscle relaxation, phosphatases other than MLCP dephosphorylate and inactivate pCPI-17 to restore MLCP activity. We show here that such hypotheses are insufficient to account for the observed rapidity of pCPI-17 inactivation in mammalian smooth muscles. Instead, MCLP itself is the critical enzyme for pCPI-17 dephosphorylation. We call the mutual sequestration mechanism through which pCPI-17 and MLCP interact inhibition by unfair competition: MLCP protects pCPI-17 from other phosphatases, while pCPI-17 blocks other substrates from MLCP's active site. MLCP dephosphorylates pCPI-17 at a slow rate that is nonetheless both sufficient and necessary to explain the speed of pCPI-17 dephosphorylation and the consequent MLCP activation during muscle relaxation.

Article and author information

Author details

  1. Joshua J Filter

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Byron C Williams

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Masumi Eto

    Department of Molecular Physiology and Biophysics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. David Shalloway

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael L Goldberg

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    For correspondence
    mlg11@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0200-0277

Funding

NIH Office of the Director (GM048430)

  • Michael L Goldberg

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Roger J Davis, University of Massachusetts Medical School, United States

Publication history

  1. Received: December 24, 2016
  2. Accepted: March 31, 2017
  3. Accepted Manuscript published: April 7, 2017 (version 1)
  4. Accepted Manuscript updated: April 12, 2017 (version 2)
  5. Accepted Manuscript updated: April 20, 2017 (version 3)
  6. Version of Record published: May 23, 2017 (version 4)

Copyright

© 2017, Filter et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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