Evidence map›Paper›PMID 25471072›Full record

ArticleThe EMBO journal2015

KSHV-TK is a tyrosine kinase that disrupts focal adhesions and induces Rho-mediated cell contraction.

Michael B Gill, Rachel Turner, Philip G Stevenson, Michael Way

Open access · greenAbstract read
In one paragraph

Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

16 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Manipulation of Focal Adhesion Signaling by Pathogenic Microbes.International journal of molecular sciences · 2021
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Kaposi sarcoma herpesvirus pathogenesis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
    Review
  14. Article
  15. Review
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Michael B GillDivision of Virology, Department of Pathology, University of Cambridge, Cambridge, UK mbg22@cam.ac.uk.
Rachel TurnerDivision of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
Philip G StevensonDivision of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
Michael WayCell Motility Laboratory, London Research Institute Cancer Research UK, London, UK.
University of Cambridge · GBCancer Research UK · GB

Funding

Cancer Research UKMedical Research Council G0701185
6 · The paper itself

Abstract

Paradoxically, the thymidine kinase (TK) encoded by Kaposi sarcoma-associated herpesvirus (KSHV) is an extremely inefficient nucleoside kinase, when compared to TKs from related herpesviruses. We now show that KSHV-TK, in contrast to HSV1-TK, associates with the actin cytoskeleton and induces extensive cell contraction followed by membrane blebbing. These dramatic changes in cell morphology depend on the auto-phosphorylation of tyrosines 65, 85 and 120 in the N-terminus of KSHV-TK. Phosphorylation of tyrosines 65/85 and 120 results in an interaction with Crk family proteins and the p85 regulatory subunit of PI3-Kinase, respectively. The interaction of Crk with KSHV-TK leads to tyrosine phoshorylation of this cellular adaptor. Auto-phosphorylation of KSHV-TK also induces a loss of FAK and paxillin from focal adhesions, resulting in activation of RhoA-ROCK signalling to myosin II and cell contraction. In the absence of FAK or paxillin, KSHV-TK has no effect on focal adhesion integrity or cell morphology. Our observations demonstrate that by acting as a tyrosine kinase, KSHV-TK modulates signalling and cell morphology.

Indexed as

AnimalsChlorocebus aethiopsCOS CellsFocal AdhesionsHeLa CellsHerpesvirus 8, HumanHumansImmunoblottingImmunoprecipitationPaxillinPhosphatidylinositol 3-KinasesPhosphorylationProtein-Tyrosine KinasesProto-Oncogene Proteins c-crkrho GTP-Binding ProteinsCRK protein, humanPaxillinPhosphatidylinositol 3-KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-crkrho GTP-Binding ProteinsCrk/PI3‐Kinasefocal adhesionKaposi sarcoma‐associated herpesvirusRhoAthymidine kinase

Identifiers

PMID25471072
PMCPMC4331000
OpenAlexW2046361245

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.