Evidence map›Paper›PMID 23585225›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013

LPS induces pp60c-src-mediated tyrosine phosphorylation of Hsp90 in lung vascular endothelial cells and mouse lung.

Nektarios Barabutis, Vaishali Handa, Christiana Dimitropoulou, Ruslan Rafikov, Connie Snead, Sanjiv Kumar, Atul Joshi, Gagan Thangjam, David Fulton, Stephen M Black and 2 more

Abstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2013. 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
1.5field-weighted citation impact, top 19% 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, 32 citations in OpenAlex.

  1. Restoration of pp60International journal of molecular sciences · 2025
    Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Autophagy, Unfolded Protein Response and Lung Disease.Current research in cell biology · 2020
    Article
  10. Article
  11. P53: The endothelium defender.Journal of cellular biochemistry · 2019
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Regulation of pulmonary endothelial barrier function by kinases.American journal of physiology. Lung cellular and molecular physiology · 2016
    Review
  20. Review
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

12 authors at 1 institution in 1 country.

Nektarios BarabutisVascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
Vaishali Handa
Christiana Dimitropoulou
Ruslan Rafikov
Connie Snead
Sanjiv Kumar
Atul Joshi
Gagan Thangjam
David Fulton
Stephen M Black
Vijay Patel
John D Catravas
Augusta University · US

Funding

Therapeutic Mechanisms of RhoA Inhibition In Acute Lung InjuryP01HL101902 · NHLBI · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2011 to 2016
$11.2M
VASCULAR ANTI-INFLAMMATORY ACTIONS OF HSP90 INHIBITORSR01HL093460 · NHLBI · OLD DOMINION UNIVERSITY · PI CATRAVAS, JOHN D · 2010 to 2013
$1.4M
NHLBI NIH HHS HL 06693NHLBI NIH HHS HL 093460NHLBI NIH HHS HL 101902NHLBI NIH HHS P01 HL101902
6 · The paper itself

Abstract

Heat shock protein 90 (Hsp90) inhibitors were initially developed as anticancer agents; however, it is becoming increasing clear that they also possess potent anti-inflammatory properties. Posttranslational modifications of Hsp90 have been reported in tumors and have been hypothesized to affect client protein- and inhibitor-binding activities. In the present study we investigated the posttranslational modification of Hsp90 in inflammation. LPS, a prototypical inflammatory agent, induced concentration- and time-dependent tyrosine (Y) phosphorylation of Hsp90α and Hsp90β in bovine pulmonary arterial and human lung microvascular endothelial cells (HLMVEC). Mass spectrometry identified Y309 as a major site of Y phosphorylation on Hsp90α (Y300 of Hsp90β). LPS-induced Hsp90 phosphorylation was prevented by the Hsp90 inhibitor 17-allyl-amino-demethoxy-geldanamycin (17-AAG) in vitro as well as in lungs from LPS-treated mice, in vivo. Furthermore, 17-AAG prevented LPS-induced pp60src activation. LPS-induced Hsp90 phosphorylation was also prevented by the pp60src inhibitor PP2. Additionally, Hsp90 phosphorylation was induced by infecting cells with a constitutively active pp60src adenovirus, whereas either a dominant-negative pp60src adenovirus or reduced expression of pp60src by a specific siRNA prevented the LPS-induced Y phosphorylation of Hsp90. Transfection of HLMVEC with the nonphosphorylatable Hsp90β Y300F mutant prevented LPS-induced Hsp90β tyrosine phosphorylation but not pp60src activation. Furthermore, the Hsp90β Y300F mutant showed a reduced ability to bind the Hsp90 client proteins eNOS and pp60src and HLMVEC transfected with the mutant exhibited reduced LPS-induced barrier dysfunction. We conclude that inflammatory stimuli cause posttranslational modifications of Hsp90 that are Hsp90-inhibitor sensitive and may be important to the proinflammatory actions of Hsp90.

Indexed as

AnimalsBenzoquinonesCattleCells, CulturedEndothelial CellsHSP90 Heat-Shock ProteinsHumansLactams, MacrocyclicLipopolysaccharidesLungMiceMice, Inbred C57BLNitric Oxide Synthase Type IIIPhosphorylationProtein BindingProtein Processing, Post-TranslationalAG 1879BenzoquinonesHSP90AA2P protein, humanHSP90AB1 protein, humanHSP90 Heat-Shock ProteinsLactams, MacrocyclicLipopolysaccharidesNitric Oxide Synthase Type IIINOS3 protein, humanProto-Oncogene Proteins pp60(c-src)PyrimidinesRNA, Small InterferingtanespimycinTyrosineendothelial cellsHsp90humanLPSposttranslational modifications

Identifiers

PMID23585225
PMCPMC3680748
OpenAlexW1975791529

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.