Evidence map›Paper›PMID 27153537›Full record

ArticleMolecular cell2016

Structural Basis for Noncanonical Substrate Recognition of Cofilin/ADF Proteins by LIM Kinases.

Stephanie Hamill, Hua Jane Lou, Benjamin E Turk, Titus J Boggon

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.6field-weighted citation impact, top 8% 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

41 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Regulation and signaling of the LIM domain kinases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. A Par3/LIM Kinase/Cofilin Pathway Mediates Human Airway Smooth Muscle Relaxation by TAS2R14.American journal of respiratory cell and molecular biology · 2023
    Article
  15. Demystifying Bitter Taste Receptor Relaxation of Airway Smooth Muscle.American journal of respiratory cell and molecular biology · 2023
    Article
  16. Article
  17. Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022
    Review
  18. Review
  19. Article
  20. Article
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.

Stephanie HamillDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
Hua Jane LouDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
Benjamin E TurkDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Titus J BoggonDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: titus.boggon@yale.edu.
Yale University · USYale Cancer Center · US

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Structure-directed investigations into the regulation of Ste20 kinasesR01GM102262 · NIGMS · YALE UNIVERSITY · PI BOGGON, TITUS JONATHON · 2012 to 2025
$4.2M
NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R01 GM102262
6 · The paper itself

Abstract

Cofilin/actin-depolymerizing factor (ADF) proteins are critical nodes that relay signals from protein kinase cascades to the actin cytoskeleton, in particular through site-specific phosphorylation at residue Ser3. This is important for regulation of the roles of cofilin in severing and stabilizing actin filaments. Consequently, cofilin/ADF Ser3 phosphorylation is tightly controlled as an almost exclusive substrate for LIM kinases. Here we determine the LIMK1:cofilin-1 co-crystal structure. We find an interface that is distinct from canonical kinase-substrate interactions. We validate this previously unobserved mechanism for high-fidelity kinase-substrate recognition by in vitro kinase assays, examination of cofilin phosphorylation in mammalian cells, and functional analysis in S. cerevisiae. The interface is conserved across all LIM kinases. Remarkably, we also observe both pre- and postphosphotransfer states in the same crystal lattice. This study therefore provides a molecular understanding of how kinase-substrate recognition acts as a gatekeeper to regulate actin cytoskeletal dynamics.

Indexed as

Binding SitesCatalytic DomainCofilin 1Crystallography, X-RayHEK293 CellsHumansLim KinasesModels, MolecularMutationPhosphorylationProtein BindingProtein ConformationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSerineStructure-Activity RelationshipCFL1 protein, humanCOF1 protein, S cerevisiaeCofilin 1LIMK1 protein, humanLim KinasesSaccharomyces cerevisiae ProteinsSerine

Identifiers

PMID27153537
PMCPMC4860616
OpenAlexW2345994268

What OpenQuestion holds

Textmetadata
LicenceTDM
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.