Evidence map›Paper›PMID 24025335›Full record

ArticleThe Journal of biological chemistry2013

Novel role for p21-activated kinase 2 in thrombin-induced monocyte migration.

Ravisekhar Gadepalli, Sivareddy Kotla, Mark R Heckle, Shailendra K Verma, Nikhlesh K Singh, Gadiparthi N Rao

RetractedOpen access · hybridAbstract readRetracted Publication
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.2field-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

23 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. GαFrontiers in cell and developmental biology · 2022
    Review
  4. Article
  5. Review
  6. Review
  7. Transcriptomic and functional studies reveal undermined chemotactic and angiostimulatory properties of aged microglia during stroke recovery.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020
    Article
  8. GαExperimental & molecular medicine · 2020
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Rac1 regulates bacterial toxin-induced thrombin generation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016
    Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Ravisekhar GadepalliFrom the Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163.
Sivareddy Kotla
Mark R Heckle
Shailendra K Verma
Nikhlesh K Singh
Gadiparthi N Rao
University of Tennessee Health Science Center · US

Funding

NFATs AND VASCULAR INJURYR01HL069908 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI RAO, GADIPARTHI N · 2002 to 2019
$5.9M
GPCR Signaling & Vascular Wall RemodelingR01HL103575 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI RAO, GADIPARTHI N · 2011 to 2019
$4.1M
NHLBI NIH HHS HL069908NHLBI NIH HHS HL103575NHLBI NIH HHS R01 HL069908NHLBI NIH HHS R01 HL103575
6 · The paper itself

Abstract

To understand the role of thrombin in inflammation, we tested its effects on migration of THP-1 cells, a human monocytic cell line. Thrombin induced THP-1 cell migration in a dose-dependent manner. Thrombin induced tyrosine phosphorylation of Pyk2, Gab1, and p115 RhoGEF, leading to Rac1- and RhoA-dependent Pak2 activation. Downstream to Pyk2, Gab1 formed a complex with p115 RhoGEF involving their pleckstrin homology domains. Furthermore, inhibition or depletion of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, or Pak2 levels substantially attenuated thrombin-induced THP-1 cell F-actin cytoskeletal remodeling and migration. Inhibition or depletion of PAR1 also blocked thrombin-induced activation of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2, resulting in diminished THP-1 cell F-actin cytoskeletal remodeling and migration. Similarly, depletion of Gα12 negated thrombin-induced Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2 activation, leading to attenuation of THP-1 cell F-actin cytoskeletal remodeling and migration. These novel observations reveal that thrombin induces monocyte/macrophage migration via PAR1-Gα12-dependent Pyk2-mediated Gab1 and p115 RhoGEF interactions, leading to Rac1- and RhoA-targeted Pak2 activation. Thus, these findings provide mechanistic evidence for the role of thrombin and its receptor PAR1 in inflammation.

Indexed as

ActinsAdaptor Proteins, Signal TransducingAnimalsCell Line, TumorCell MovementCytoskeletonEnzyme ActivationFocal Adhesion Kinase 2HumansMacrophagesMiceMonocytesNeuropeptidesp21-Activated KinasesPhosphoproteinsrac1 GTP-Binding ProteinActinsAdaptor Proteins, Signal TransducingFocal Adhesion Kinase 2GAB1 protein, humanGab1 protein, mouseNeuropeptidesp21-Activated KinasesPAK2 protein, humanPak2 protein, mousePhosphoproteinsPTK2B protein, humanPtk2b protein, mouserac1 GTP-Binding ProteinRAC1 protein, humanRac1 protein, mouserhoA GTP-Binding ProteinRHOA protein, humanRhoA protein, mouserho GTP-Binding ProteinsRho Guanine Nucleotide Exchange FactorsThrombinG Protein-coupled Receptors (GPCRs)InflammationMacrophagesMigrationSignaling

Identifiers

PMID24025335
PMCPMC3829397
OpenAlexW2034995931

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.