Evidence map›Paper›PMID 25525271›Full record

ArticleThe Journal of biological chemistry2015

Epidermal growth factor activates the Rho GTPase-activating protein (GAP) Deleted in Liver Cancer 1 via focal adhesion kinase and protein phosphatase 2A.

Archna Ravi, Shelly Kaushik, Aarthi Ravichandran, Catherine Qiurong Pan, Boon Chuan Low

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

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  7. fMLP-dependent activation of Akt and ERK1/2 through ROS/Rho A pathways is mediated through restricted activation of the FPRL1 (FPR2) receptor.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018
    Article
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  11. Calcineurin, the CaMolecular biology of the cell · 2017
    Article
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  14. Regulating Rho GTPases and their regulators.Nature reviews. Molecular cell biology · 2016
    Review
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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

5 authors at 1 institution in 1 country.

Archna RaviFrom the Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543 Singapore and the Mechanobiology Institute, National University of Singapore, 5A Engineering Drive, 117411 Singapore.
Shelly KaushikFrom the Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543 Singapore and the Mechanobiology Institute, National University of Singapore, 5A Engineering Drive, 117411 Singapore.
Aarthi Ravichandranthe Mechanobiology Institute, National University of Singapore, 5A Engineering Drive, 117411 Singapore.
Catherine Qiurong Panthe Mechanobiology Institute, National University of Singapore, 5A Engineering Drive, 117411 Singapore.
Boon Chuan LowFrom the Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543 Singapore and the Mechanobiology Institute, National University of Singapore, 5A Engineering Drive, 117411 Singapore dbslowbc@nus.edu.sg.
National University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deleted in Liver Cancer 1 (DLC1) is a RHO GTPase-activating protein (GAP) that negatively regulates RHO. Through its GAP activity, it modulates the actin cytoskeleton network and focal adhesion dynamics, ultimately leading to suppression of cell invasion and metastasis. Despite its presence in various structural and signaling components, little is known about how the activity of DLC1 is regulated at focal adhesions. Here we show that EGF stimulation activates the GAP activity of DLC1 through a concerted mechanism involving DLC1 phosphorylation by MEK/ERK and its subsequent dephosphorylation by protein phosphatase 2A (PP2A) and inhibition of focal adhesion kinase by MEK/ERK to allow the binding between DLC1 and PP2A. Phosphoproteomics and mutation studies revealed that threonine 301 and serine 308 on DLC1, known previously to be mutated in certain cancers, are required for DLC1-PP2A interaction and the subsequent activation of DLC1 upon their dephosphorylation. The intricate interplay of this "MEK/ERK-focal adhesion kinase-DLC1-PP2A" quartet provides a novel checkpoint in the spatiotemporal control of cell spreading and cell motility.

Indexed as

Blotting, WesternCell MovementCell ProliferationEpidermal Growth FactorFocal Adhesion Kinase 1Focal AdhesionsGTPase-Activating ProteinsHEK293 CellsHeLa CellsHumansImmunoprecipitationMAP Kinase Kinase 1Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphorylationProtein Phosphatase 2DLC1 protein, humanEpidermal Growth FactorFocal Adhesion Kinase 1GTPase-Activating ProteinsMAPK1 protein, humanMAP Kinase Kinase 1Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Protein Phosphatase 2ProteomePTK2 protein, humanTumor Suppressor ProteinsDeleted In Liver Cancer 1 (DLC1)Focal Adhesion Kinase (FAK)GTPase-activating Protein (GAP)MEK/ERKPhosphorylationProtein Phosphatase 2 (PP2A)PTK2 Protein-tyrosine Kinase 2 (PTK2)

Identifiers

PMID25525271
PMCPMC4326825
OpenAlexW2018306020

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.