Evidence map›Paper›PMID 12842009›Full record

ArticleCurrent biology : CB2003

Rnd proteins function as RhoA antagonists by activating p190 RhoGAP.

Krister Wennerberg, Marie-Annick Forget, Shawn M Ellerbroek, William T Arthur, Keith Burridge, Jeffrey Settleman, Channing J Der, Steen H Hansen

Abstract readComparative Study
In one paragraph

Article in Current biology : CB, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.

0numbers the graph read from it
0cells of the map it votes in
110citing 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

110 citing papers in PubMed, 238 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Article
  6. Functions of RhoA in the female reproductive system.Reproductive and developmental medicine · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Emerging functions of pseudoenzymes.The Biochemical journal · 2023
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Selectivity Determinants of RHO GTPase Binding to IQGAPs.International journal of molecular sciences · 2021
    Article
  19. Article
  20. Article

50 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

8 authors at 3 institutions in 1 country.

Krister WennerbergDepartment of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Marie-Annick Forget
Shawn M Ellerbroek
William T Arthur
Keith Burridge
Jeffrey Settleman
Channing J Der
Steen H Hansen
University of North Carolina at Chapel Hill · USBoston Biomedical Research Institute · USMassachusetts General Hospital · US

Funding

STRUCTURE/FUNCTION OF FOCAL ADHESIONSR01GM029860 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BURRIDGE, KEITH · 1985 to 2018
$6.7M
Regulation and Functin of the p190 RhoGAPsR01CA062142 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI SETTLEMAN, JEFFREY E · 1994 to 2006
$2.5M
Rnd Effector Molecules in Epithelial Cell TransformationR01CA092354 · NCI · BOSTON CHILDREN'S HOSPITAL · PI HANSEN, STEEN HENNING · 2003 to 2007
$2.2M
RHO FAMILY PROTEINS AND MALIGNANT TRANSFORMATIONR01CA063071 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J · 1994 to 2007
$2.0M
NCI NIH HHS R01 CA062142NCI NIH HHS R01 CA063071NCI NIH HHS R01 CA092354NCI NIH HHS R01 CA62142NCI NIH HHS R01 CA63071NIGMS NIH HHS R01 GM029860NIGMS NIH HHS R01 GM29860
6 · The paper itself

Abstract

backgroundThe Rnd proteins Rnd1, Rnd2, and Rnd3 (RhoE) comprise a unique branch of Rho-family G-proteins that lack intrinsic GTPase activity and consequently remain constitutively "active." Prior studies have suggested that Rnd proteins play pivotal roles in cell regulation by counteracting the biological functions of the RhoA GTPase, but the molecular basis for this antagonism is unknown. Possible mechanisms by which Rnd proteins could function as RhoA antagonists include sequestration of RhoA effector molecules, inhibition of guanine nucleotide exchange factors, and activation of GTPase-activating proteins (GAPs) for RhoA. However, effector molecules of Rnd proteins with such properties have not been identified.

resultsHere we identify p190 RhoGAP (p190), the most abundant GAP for RhoA in cells, as an interactor with Rnd proteins and show that this interaction is mediated by a p190 region that is distinct from the GAP domain. Using Rnd3-RhoA chimeras and Rnd3 mutants defective in p190 binding, as well as p190-deficient cells, we demonstrate that the cellular effects of Rnd expression are mediated by p190. We moreover show that Rnd proteins increase the GAP activity of p190 toward GTP bound RhoA and, finally, demonstrate that expression of Rnd3 leads to reduced cellular levels of RhoA-GTP by a p190-dependent mechanism.

conclusionsOur results identify p190 RhoGAPs as effectors of Rnd proteins and demonstrate a novel mechanism by which Rnd proteins function as antagonists of RhoA.

Indexed as

Signal Transduction3T3 CellsAnimalsChlorocebus aethiopsCOS CellsDNA-Binding ProteinsGene ExpressionGTPase-Activating ProteinsGuanine Nucleotide Exchange FactorsMiceMicroscopy, FluorescenceNuclear ProteinsPrecipitin TestsRepressor ProteinsrhoA GTP-Binding Proteinrho GTP-Binding ProteinsArhgap35 protein, mouseArhgap5 protein, mouseDNA-Binding ProteinsGTPase-Activating ProteinsGuanine Nucleotide Exchange FactorsNuclear ProteinsRepressor ProteinsrhoA GTP-Binding Proteinrho GTPase-activating proteinrho GTP-Binding ProteinsRND3 protein, humanRnd3 protein, mouse

Identifiers

PMID12842009
PMCPMC6918695
OpenAlexW2071614175

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.