Evidence map›Paper›PMID 15940262›Full record

ArticleOncogene2005

Annexin A6 stimulates the membrane recruitment of p120GAP to modulate Ras and Raf-1 activity.

Thomas Grewal, Rachael Evans, Carles Rentero, Francesc Tebar, Laia Cubells, Iñaki de Diego, Matthias F Kirchhoff, William E Hughes, Joerg Heeren, Kerry-Anne Rye and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

46 citing papers in PubMed, 89 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Annexin Animal Models-From Fundamental Principles to Translational Research.International journal of molecular sciences · 2021
    Review
  8. Article
  9. Review
  10. Article
  11. Annexins in Adipose Tissue: Novel Players in Obesity.International journal of molecular sciences · 2019
    Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Annexins-Coordinators of Cholesterol Homeostasis in Endocytic Pathways.International journal of molecular sciences · 2018
    Review
  17. Article
  18. Article
  19. 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

14 authors at 7 institutions in 3 countries.

Thomas GrewalCentre for Immunology, St Vincent's Hospital. University of New South Wales, Australia.
Rachael Evans
Carles Rentero
Francesc Tebar
Laia Cubells
Iñaki de Diego
Matthias F Kirchhoff
William E Hughes
Joerg Heeren
Kerry-Anne Rye
Franz Rinninger
Roger J Daly
Albert Pol
Carlos Enrich
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESGarvan Institute of Medical Research · AUSt Vincent's Hospital · AUUniversitat de Barcelona · ESUniversität Hamburg · DEEppendorf (Germany) · DEThe Heart Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Annexin A6 is a calcium-dependent membrane-binding protein that interacts with signalling proteins, including the GTPase-activating protein p120GAP, one of the most important inactivators of Ras. Since we have demonstrated that annexin A6 inhibits EGF- and TPA-induced Ras signalling, we investigated whether modulation of Ras activity by annexin A6 was mediated via altered subcellular localization of p120GAP. First, we exploited our observation that high-density lipoproteins (HDL) can activate the Ras/MAP kinase pathway. Expression of annexin A6 caused a significant reduction in HDL-induced activation of Ras and Raf-1. Annexin A6 promoted membrane binding of p120GAP in vitro, and plasma membrane targeting of p120GAP in living cells, both in a Ca(2+)-dependent manner, which is consistent with annexin A6 promoting the Ca(2+)-dependent assembly of p120GAP-Ras at the plasma membrane. We then extended these studies to other cell types and stimuli. Expression of annexin A6 in A431 cells reduced, while RNAi-mediated suppression of annexin A6 in HeLa cells enhanced EGF-induced Ras and Erk activation. Importantly, the enhancement of Ras activation following RNAi-mediated reduction in p120GAP levels was more marked in annexin A6-expressing A431 cells than controls, indicating that the effect of annexin A6 on Ras was mediated via p120GAP. Finally, we demonstrated that annexin A6 promotes plasma membrane targeting of p120GAP in A431 cells in response to a variety of stimuli, resulting in colocalization with H-Ras. These findings demonstrate an important role for annexin A6 in regulating plasma membrane localization of p120GAP and hence Ras activity.

Indexed as

AnimalsAnnexin A6CalciumCell MembraneCHO CellsCholesterol, HDLCricetinaeCricetulusEnzyme ActivationEpidermal Growth FactorFluorescent Antibody TechniqueHeLa CellsHumansImmunoprecipitationp120 GTPase Activating ProteinProtein TransportAnnexin A6CalciumCholesterol, HDLEpidermal Growth FactorHRAS protein, humanp120 GTPase Activating ProteinProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)

Identifiers

PMID15940262
OpenAlexW2037083050

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.