Evidence map›Paper›PMID 22327215›Full record

ArticleThe EMBO journal2012

Axl is essential for VEGF-A-dependent activation of PI3K/Akt.

Guo-Xiang Ruan, Andrius Kazlauskas

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

134 citing papers in PubMed, 218 citations in OpenAlex.

  1. Trial
  2. Review
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  12. Recent advances in TAM mechanisms in lung diseases.Journal of translational medicine · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. AXL promotes lymphangiogenesis by amplifying VEGF-C-mediated AKT pathway.Cellular and molecular life sciences : CMLS · 2025
    Article
  19. AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025
    Review
  20. Review

74 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 1 country.

Guo-Xiang RuanSchepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Andrius Kazlauskas
Harvard University · USSmith-Kettlewell Eye Research Institute · US

Funding

Understanding vessel regressionR03EY016385 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI KAZLAUSKAS, ANDRIUS · 2005 to 2007
$578k
NEI NIH HHS EY016385NEI NIH HHS R03 EY016385
6 · The paper itself

Abstract

Herein, we report that vascular endothelial growth factor A (VEGF-A) engages the PI3K/Akt pathway by a previously unknown mechanism that involves three tyrosine kinases. Upon VEGF-A-dependent activation of VEGF receptor-2 (VEGFR-2), and subsequent TSAd-mediated activation of Src family kinases (SFKs), SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand-independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt. Other VEGF-A-mediated signalling pathways are independent of Axl. Interfering with Axl expression or function impairs VEGF-A- but not bFGF-dependent migration of endothelial cells. Similarly, Axl null mice respond poorly to VEGF-A-induced vascular permeability or angiogenesis, whereas other agonists induce a normal response. These results elucidate the mechanism by which VEGF-A activates PI3K/Akt, and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes.

Indexed as

Amino Acid MotifsAnimalsAxl Receptor Tyrosine KinaseCell MovementEndothelial CellsFibroblast Growth Factor 2MiceMice, KnockoutNeovascularization, PhysiologicPhosphatidylinositol 3-KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Axl Receptor Tyrosine KinaseAXL receptor tyrosine kinase, mouseFibroblast Growth Factor 2Phosphatidylinositol 3-KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID22327215
PMCPMC3321201
OpenAlexW1876403508

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.