Evidence map›Paper›PMID 14629200›Full record

ArticleThe Biochemical journal2004

An activating mutant of Rac1 that fails to interact with Rho GDP-dissociation inhibitor stimulates membrane ruffling in mammalian cells.

Payal N Gandhi, Richard M Gibson, Xiaofeng Tong, Jun Miyoshi, Yoshimi Takai, Martha Konieczkowski, John R Sedor, Amy L Wilson-Delfosse

Open access · bronzeAbstract read
In one paragraph

Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.8field-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

20 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Computational analysis of Rho GTPase cycling.PLoS computational biology · 2013
    Article
  10. Article
  11. The 'invisible hand': regulation of RHO GTPases by RHOGDIs.Nature reviews. Molecular cell biology · 2011
    Review
  12. Article
  13. Diacylglycerol kinase alpha mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI.Proceedings of the National Academy of Sciences of the United States of America · 2010
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review
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 2 institutions in 1 country.

Payal N GandhiDepartment of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Richard M Gibson
Xiaofeng Tong
Jun Miyoshi
Yoshimi Takai
Martha Konieczkowski
John R Sedor
Amy L Wilson-Delfosse
Osaka Medical Center for Cancer and Cardiovascular Diseases · JPOsaka University · JP

Funding

PREDOCTORAL TRAINING PROGRAM IN MOLECULAR THERAPEUTICST32GM008803 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI MIEYAL, JOHN J, NIEMAN, MARVIN THOMAS · 2001 to 2023
$4.2M
TARGETING RENAL OUTER MEDULLARY K+ CHANNEL ROMK FOR NEW CLASS OF DIURETICSP50DK054178 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI CARLIN, CATHLEEN R · 1998 to 2002
$2.2M
MECHANISMS OF GLOMERULAR INJURYR01DK038558 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI SEDOR, JOHN R. · 1987 to 1998
–
NIDDK NIH HHS DK 38558NIDDK NIH HHS P50 DK54178NIGMS NIH HHS T32 GM008803
6 · The paper itself

Abstract

Rac1, a member of the Rho family of small GTP-binding proteins, is involved in the regulation of the actin cytoskeleton via activation of lamellipodia and membrane ruffle formation. RhoGDI (Rho-family-specific GDP-dissociation inhibitor) forms a complex with Rho proteins in the cytosol of mammalian cells. It not only regulates guanine nucleotide binding to Rho proteins, but may also function as a molecular shuttle to carry Rho proteins from an inactive cytosolic pool to the membrane for activation. These studies tested if RhoGDI is necessary for the translocation of Rac1 from the cytosol to the plasma membrane for the formation of membrane ruffles. We describe a novel mutant of Rac1, R66E (Arg66-->Glu), that fails to bind RhoGDI. This RhoGDI-binding-defective mutation is combined with a Rac1-activating mutation G12V, resulting in a double-mutant [Rac1(G12V/R66E)] that fails to interact with RhoGDI in COS-7 cells, but remains constitutively activated. This double mutant stimulates membrane ruffling to a similar extent as that observed after epidermal growth factor treatment of non-transfected cells. To confirm that Rac1 can signal ruffle formation in the absence of interaction with RhoGDI, Rac1(G12V) was overexpressed in cultured mesangial cells derived from a RhoGDI knockout mouse. Rac1-mediated membrane ruffling was indistinguishable between the RhoGDI(-/-) and RhoGDI(+/+) cell lines. In both the COS-7 and cultured mesangial cells, Rac1(G12V) and Rac1(G12V/R66E) co-localize with membrane ruffles. These findings suggest that interaction with RhoGDI is not essential in the mechanism by which Rac1 translocates to the plasma membrane to stimulate ruffle formation.

Indexed as

AnimalsCell LineCell MembraneChlorocebus aethiopsCOS CellsEnzyme ActivationGlomerular MesangiumGuanine Nucleotide Dissociation InhibitorsMiceMice, KnockoutModels, BiologicalMutationProtein Transportrac1 GTP-Binding ProteinRecombinant Fusion Proteinsrho-Specific Guanine Nucleotide Dissociation InhibitorsGuanine Nucleotide Dissociation Inhibitorsrac1 GTP-Binding ProteinRecombinant Fusion Proteinsrho-Specific Guanine Nucleotide Dissociation Inhibitors

Identifiers

PMID14629200
PMCPMC1223982
OpenAlexW2027908318

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.