Evidence map›Paper›PMID 19692574›Full record

ArticleMolecular biology of the cell2009

Protein tyrosine phosphatase epsilon regulates integrin-mediated podosome stability in osteoclasts by activating Src.

Shira Granot-Attas, Chen Luxenburg, Eynat Finkelshtein, Ari Elson

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

23 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Review
  3. Osteoclast Methods in Protein Phosphatase Research.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  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 1 institution in 1 country.

Shira Granot-AttasDepartment of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Chen Luxenburg
Eynat Finkelshtein
Ari Elson
Weizmann Institute of Science · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The nonreceptor isoform of tyrosine phosphatase epsilon (cyt-PTPe) supports osteoclast adhesion and activity in vivo, leading to increased bone mass in female mice lacking PTPe (EKO mice). The structure and organization of the podosomal adhesion structures of EKO osteoclasts are abnormal; the molecular mechanism behind this is unknown. We show here that EKO podosomes are disorganized, unusually stable, and reorganize poorly in response to physical contact. Phosphorylation and activities of Src, Pyk2, and Rac are decreased and Rho activity is increased in EKO osteoclasts, suggesting that integrin signaling is defective in these cells. Integrin activation regulates cyt-PTPe by inducing Src-dependent phosphorylation of cyt-PTPe at Y638. This phosphorylation event is crucial because wild-type-but not Y638F-cyt-PTPe binds and further activates Src and restores normal stability to podosomes in EKO osteoclasts. Increasing Src activity or inhibiting Rho or its downstream effector Rho kinase in EKO osteoclasts rescues their podosomal stability phenotype, indicating that cyt-PTPe affects podosome stability by functioning upstream of these molecules. We conclude that cyt-PTPe participates in a feedback loop that ensures proper Src activation downstream of integrins, thus linking integrin signaling with Src activation and accurate organization and stability of podosomes in osteoclasts.

Indexed as

AnimalsCell AdhesionCell Surface ExtensionsCytoplasmEnzyme ActivationFeedback, PhysiologicalFemaleFocal Adhesion Kinase 2IntegrinsMiceMice, KnockoutMutagenesis, Site-DirectedNeuropeptidesOsteoclastsPhosphorylationProtein Processing, Post-TranslationalFocal Adhesion Kinase 2IntegrinsNeuropeptidesProto-Oncogene Proteins pp60(c-src)Ptk2b protein, mousePtpre protein, mouserac1 GTP-Binding ProteinRac1 protein, mouserac GTP-Binding ProteinsReceptor-Like Protein Tyrosine Phosphatases, Class 4Recombinant Fusion ProteinsrhoA GTP-Binding ProteinRhoA protein, mouserho-Associated Kinasesrho GTP-Binding Proteinssrc-Family Kinases

Identifiers

PMID19692574
PMCPMC2762143
OpenAlexW2142960464

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.