Evidence map›Paper›PMID 14724572›Full record

ArticleOncogene2004

Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38.

Laurent Lamalice, François Houle, Guillaume Jourdan, Jacques Huot

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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

87 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.

  1. Pooled it
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  3. Review
  4. Review
  5. Review
  6. Review
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    Article
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  19. Review
  20. Review

27 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

4 authors at 2 institutions in 1 country.

Laurent LamaliceLe Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, 9 rue McMahon, Québec, Canada G1R 2J6.
François Houle
Guillaume Jourdan
Jacques Huot
Université Laval · CAHôtel-Dieu de Québec · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Activation of the tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) by VEGF leads to the activation of stress-activated protein kinase (SAPK)2/p38 and then to actin polymerization and reorganization into stress fibers in endothelial cells. In turn, this triggers endothelial cell migration. Yet, nothing is known about the molecular mechanisms that couple VEGFR2 to SAPK2/p38. Here, we found that VEGF increased by twofold the activity of the small GTPase Cdc42 and that the expression of two different constitutively active forms of Cdc42 (Cdc42 V12 and Cdc42 L61) led to a marked increase in the formation of stress fibers that was sensitive to SAPK2/p38 inhibition by SB203580. Moreover, the expression of a dominant-negative form of Cdc42 (Cdc42 N17) inhibited the activation of SAPK2/p38 and of its direct target MAP kinase-activated protein kinase 2. These results indicate that Cdc42 is upstream of SAPK2/p38 in response to the activation of VEGFR2 by VEGF. In contrast, we found that neither RhoA nor Rac was involved in the SAPK2/p38-mediated actin reorganization induced by VEGF. Using a site-specific mutant of the major autophosphorylation site Y1214 on VEGFR2, we found that the mutant Y1214F inhibited the activation of both Cdc42 and SAPK2/p38 in response to VEGF. We conclude that phosphorylation of Y1214 on VEGFR2 is required to trigger the sequential activation of Cdc42 and SAPK2/p38 and to drive the SAPK2/p38-mediated actin remodeling in stress fibers in endothelial cells exposed to VEGF.

Indexed as

Actinscdc42 GTP-Binding ProteinCells, CulturedEnzyme ActivationHumansMitogen-Activated Protein KinasesModels, Biologicalp38 Mitogen-Activated Protein KinasesPhosphorylationPhosphotyrosinerac1 GTP-Binding ProteinrhoA GTP-Binding ProteinSignal TransductionStress FibersVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Actinscdc42 GTP-Binding ProteinMitogen-Activated Protein Kinasesp38 Mitogen-Activated Protein KinasesPhosphotyrosinerac1 GTP-Binding ProteinrhoA GTP-Binding ProteinVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID14724572
OpenAlexW2004131152

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.