Evidence map›Paper›PMID 20042605›Full record

ArticleThe Journal of biological chemistry2010

Basis for the isoform-specific interaction of myosin phosphatase subunits protein phosphatase 1c beta and myosin phosphatase targeting subunit 1.

Elizabeth Scotto-Lavino, Miguel Garcia-Diaz, Guangwei Du, Michael A Frohman

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
0.9field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Frontotemporal Lobar Dementia Mutant Tau Impairs Axonal Transport through a Protein Phosphatase 1γ-Dependent Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  7. Article
  8. Article
  9. Article
  10. Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics.Biochimica et biophysica acta. Molecular cell research · 2019
    Review
  11. Article
  12. SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  13. Article
  14. Overexpression of Myosin Phosphatase Target Subunit 1 (MYPT1) Inhibits Tumor Progression and Metastasis of Gastric Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2018
    Article
  15. Article
  16. Review
  17. Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Elizabeth Scotto-LavinoDepartment of Pharmacology, Stony Brook University, Stony Brook, New York 11794-5140, USA.
Miguel Garcia-Diaz
Guangwei Du
Michael A Frohman
Stony Brook University · USThe University of Texas Health Science Center at Houston · US

Funding

Lipid-signaling pathways regulating mitochondrial morphology, energetics, and movR01GM084251 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI FROHMAN, MICHAEL A. · 2009 to 2017
$2.6M
Roles of Phospholipase D in AT1 Receptor EndocytosisR01GM071475 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI DU, GUANGWEI · 2006 to 2010
$1.6M
Role of Phospholipase D1 in regulated exocytosisR01GM071520 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI FROHMAN, MICHAEL A. · 2006 to 2009
$1.3M
NIGMS NIH HHS GM071475NIGMS NIH HHS GM071520NIGMS NIH HHS GM084251NIGMS NIH HHS R01 GM071475NIGMS NIH HHS R01 GM071520NIGMS NIH HHS R01 GM084251
6 · The paper itself

Abstract

Myosin II association with actin, which triggers contraction, is regulated by orchestrated waves of phosphorylation/dephosphorylation of the myosin regulatory light chain. Blocking myosin regulatory light chain phosphorylation with small molecule inhibitors alters the shape, adhesion, and migration of many types of smooth muscle and cancer cells. Dephosphorylation is mediated by myosin phosphatase (MP), a complex that consists of a catalytic subunit (protein phosphatase 1c, PP1c), a large subunit (myosin phosphatase targeting subunit, MYPT), and a small subunit of unknown function. MYPT functions by targeting PP1c onto its substrate, phosphorylated myosin II. Using RNA interference, we show here that stability of PP1c beta and MYPT1 is interdependent; knocking down one of the subunits decreases the expression level of the other. Associated changes in cell shape also occur, characterized by flattening and spreading accompanied by increased cortical actin, and cell numbers decrease secondary to apoptosis. Of the three highly conserved isoforms of PP1c, we show that MYPT1 binding is restricted to PP1c beta, and, using chimeric analysis and site-directed mutations, that the central region of PP1c beta confers the isoform-specific binding. This finding was unexpected because the MP crystal structure has been solved and was reported to identify the variable, C-terminal domain of PP1c beta as being the region key for isoform-specific interaction with MYPT1. These findings suggest a potential screening strategy for cardiovascular and cancer therapeutic agents based on destabilizing MP complex formation and function.

Indexed as

AnimalsCHO CellsCricetinaeCricetulusGene Expression RegulationIsoenzymesMutagenesis, Site-DirectedMyosin-Light-Chain PhosphataseMyosin Light ChainsPhosphorylationProtein BindingProtein Phosphatase 1Protein StabilityProtein SubunitsIsoenzymesMyosin-Light-Chain PhosphataseMyosin Light ChainsProtein Phosphatase 1Protein Subunits

Identifiers

PMID20042605
PMCPMC2825437
OpenAlexW1969504295

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.