Evidence map›Paper›PMID 22469974›Full record

ArticleOncogene2013

PKCα phosphorylation of RhoGDI2 at Ser31 disrupts interactions with Rac1 and decreases GDI activity.

E M Griner, M E A Churchill, D L Brautigan, D Theodorescu

Open access · bronzeAbstract read
In one paragraph

Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Regulating Rho GTPases and their regulators.Nature reviews. Molecular cell biology · 2016
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. The faces and friends of RhoGDI2.Cancer metastasis reviews · 2012
    Review
  14. Article
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 3 institutions in 1 country.

E M GrinerDepartment of Microbiology, Immunology and Cancer Biology, Center for Cell Signaling, University of Virginia, Charlottesville, VA, USA.
M E A Churchill
D L Brautigan
D Theodorescu
University of Virginia · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Understanding the RhoGDI2 metastasis suppressor geneR01CA143971 · NCI · UNIVERSITY OF COLORADO DENVER · PI THEODORESCU, DAN · 2010 to 2020
$4.4M
Molecular Mechanism of Histone H3/H4 Chaperone FunctionR01GM079154 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI CHURCHILL, MAIR E · 2007 to 2010
$1.3M
NCI NIH HHS CA143971NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA143971NIGMS NIH HHS R01 GM079154
6 · The paper itself

Abstract

Rho family GTPases control a diverse range of cellular processes, and their deregulation has been implicated in human cancer. Guanine nucleotide dissociation inhibitors (GDIs) bind and sequester GTPases in the cytosol, restricting their actions. RhoGDI2 is a member of the GDI family that acts as a metastasis suppressor in a variety of cancer types; however, very little is known about the regulation of this protein. Here, we present a mechanism for inactivation of RhoGDI2 via protein kinase C (PKC) phosphorylation of Ser31 in a region that contacts GTPases. In cells, RhoGDI2 becomes rapidly phosphorylated at Ser31 in response to phorbol 12-myristate 13-acetate stimulation. Based on the effects of pharmacological inhibitors and knockdown by siRNA, we determine that conventional type PKCα is responsible for this phosphorylation. Phospho-mimetic S31E-RhoGDI2 exhibits reduced binding to Rac1 relative to wild type, with a concomitant failure to reduce levels of activated endogenous Rac1 or remove Rac1 from membranes. These results reveal a mechanism of downregulation of RhoGDI2 activity through PKC-mediated phosphorylation of Ser31. We hypothesize that this mechanism may serve to neutralize RhoGDI2 function in tumors that express RhoGDI2 and active PKCα.

Indexed as

Amino Acid SequenceHEK293 CellsHumansModels, MolecularPhosphorylationProtein Kinase C-alpharac1 GTP-Binding Proteinrho Guanine Nucleotide Dissociation Inhibitor betaSerineTetradecanoylphorbol AcetateTransfectionARHGDIB protein, humanphorbolol myristate acetateProtein Kinase C-alpharac1 GTP-Binding ProteinRAC1 protein, humanrho Guanine Nucleotide Dissociation Inhibitor betaSerineTetradecanoylphorbol Acetate

Identifiers

PMID22469974
PMCPMC3578973
OpenAlexW2050619260

What OpenQuestion holds

Textmetadata
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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.