Evidence map›Paper›PMID 25086068›Full record

ArticleJournal of cell science2014

Differences in binding to the ILK complex determines kindlin isoform adhesion localization and integrin activation.

Clotilde Huet-Calderwood, Nina N Brahme, Nikit Kumar, Amy L Stiegler, Srikala Raghavan, Titus J Boggon, David A Calderwood

Open access · greenAbstract read
In one paragraph

Article in Journal of cell science, 2014. 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
4.1field-weighted citation impact, top 5% 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, 62 citations in OpenAlex.

  1. ILK binding to β1 integrin is indirect and mediated by kindlin-2.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  8. Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022
    Review
  9. Article
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  12. Initiation of focal adhesion assembly by talin and kindlin: A dynamic view.Protein science : a publication of the Protein Society · 2021
    Review
  13. Article
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  19. Chapter 22: Structural and signaling functions of integrins.Biochimica et biophysica acta. Biomembranes · 2020
    Review
  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

7 authors at 1 institution in 2 countries.

Clotilde Huet-CalderwoodDepartment of Pharmacology, Yale University, New Haven, CT 06520, USA.
Nina N BrahmeDepartment of Cell Biology, Yale University, New Haven, CT 06520, USA.
Nikit KumarDepartment of Cell Biology, Yale University, New Haven, CT 06520, USA.
Amy L StieglerDepartment of Pharmacology, Yale University, New Haven, CT 06520, USA.
Srikala RaghavanDepartment of Pharmacology, Yale University, New Haven, CT 06520, USA Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Karnataka 560065, India.
Titus J BoggonDepartment of Pharmacology, Yale University, New Haven, CT 06520, USA.
David A CalderwoodDepartment of Pharmacology, Yale University, New Haven, CT 06520, USA Department of Cell Biology, Yale University, New Haven, CT 06520, USA david.calderwood@yale.edu.
Yale University · US

Funding

Skill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0M
Integrin-Filamin Interactions in Migration and SignalingR01GM068600 · NIGMS · YALE UNIVERSITY · PI CALDERWOOD, DAVID A · 2003 to 2016
$4.4M
Structure and function of the integrin-linked kinase-PINCH-parvin complexR01GM088240 · NIGMS · YALE UNIVERSITY · PI BOGGON, TITUS JONATHON, CALDERWOOD, DAVID A · 2009 to 2012
$1.4M
NIGMS NIH HHS R01 GM068600NIGMS NIH HHS R01GM068600NIGMS NIH HHS R01 GM088240NIGMS NIH HHS R01GM088240NIGMS NIH HHS T32 GM007223NIGMS NIH HHS T32GM007223
6 · The paper itself

Abstract

Kindlins are essential FERM-domain-containing focal adhesion (FA) proteins required for proper integrin activation and signaling. Despite the widely accepted importance of each of the three mammalian kindlins in cell adhesion, the molecular basis for their function has yet to be fully elucidated, and the functional differences between isoforms have generally not been examined. Here, we report functional differences between kindlin-2 and -3 (also known as FERMT2 and FERMT3, respectively); GFP-tagged kindlin-2 localizes to FAs whereas kindlin-3 does not, and kindlin-2, but not kindlin-3, can rescue α5β1 integrin activation defects in kindlin-2-knockdown fibroblasts. Using chimeric kindlins, we show that the relatively uncharacterized kindlin-2 F2 subdomain drives FA targeting and integrin activation. We find that the integrin-linked kinase (ILK)-PINCH-parvin complex binds strongly to the kindlin-2 F2 subdomain but poorly to that of kindlin-3. Using a point-mutated kindlin-2, we establish that efficient kindlin-2-mediated integrin activation and FA targeting require binding to the ILK complex. Thus, ILK-complex binding is crucial for normal kindlin-2 function and differential ILK binding contributes to kindlin isoform specificity.

Indexed as

Amino Acid SequenceAnimalsCHO CellsCricetulusFocal AdhesionsHEK293 CellsHumansIntegrinsMembrane ProteinsMiceMolecular Sequence DataNeoplasm ProteinsNIH 3T3 CellsProtein IsoformsProtein Serine-Threonine KinasesScaffold Protein ILKFERMT3 protein, humanIntegrinsMembrane ProteinsNeoplasm ProteinsProtein IsoformsProtein Serine-Threonine KinasesScaffold Protein ILKFocal adhesionIntegrinIntegrin activationIntegrin-linked kinaseKindlin

Identifiers

PMID25086068
PMCPMC4179494
OpenAlexW2318179377

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.