Evidence map›Paper›PMID 14712228›Full record

ArticleOncogene2004

Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential.

Hiroki Chikumi, Ana Barac, Babak Behbahani, Yuan Gao, Hidemi Teramoto, Yi Zheng, J Silvio Gutkind

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 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

63 citing papers in PubMed, 125 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Characterization and computational simulation of human Syx, a RhoGEF implicated in glioblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  10. Article
  11. Structural basis for p50RhoGAP BCH domain-mediated regulation of Rho inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  12. Article
  13. Arhgef1 Plays a Vital Role in Platelet Function and Thrombogenesis.Journal of the American Heart Association · 2019
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Regulating Rho GTPases and their regulators.Nature reviews. Molecular cell biology · 2016
    Review
  19. Article
  20. Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article

3 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

7 authors at 3 institutions in 1 country.

Hiroki ChikumiOral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4340, USA.
Ana Barac
Babak Behbahani
Yuan Gao
Hidemi Teramoto
Yi Zheng
J Silvio Gutkind
National Institutes of Health · USNational Institute of Dental and Craniofacial Research · USCincinnati Children's Hospital Medical Center · US

Funding

Molecular Mechanisms Of Growth Control And CarcinogenesisZIADE000551 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI GUTKIND, JORGE SILVIO · 2009 to 2015
$11.5M
ROLE OF G PROTEINS IN GROWTH CONTROL AND CARCINOGENESISZ01DE000551 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI GUTKIND, J · 1992 to 2008
$3.4M
6 · The paper itself

Abstract

PDZ-RhoGEF, LARG, and p115RhoGEF are members of a newly identified family of Rho-guanine nucleotide exchange factors (GEFs) exhibiting a unique structural feature consisting of the presence of an area of similarity to regulators of G protein signaling (RGS). This RGS-like (RGL) domain provides a functional motif by which Galpha(12) and Galpha(13) can bind and regulate the activity of these RhoGEFs, thus providing a direct link from these heterotrimeric G proteins to Rho. PDZ-RhoGEF and LARG can also be phosphorylated by tyrosine kinases, including FAK, and associate with Plexin B, a semaphorin receptor, which controls axon guidance during development, through their PDZ domain, thereby stimulating Rho. Interestingly, while characterizing a PDZ-RhoGEF antiserum, we found that a transfected PDZ-RhoGEF construct associated with the endogenous PDZ-RhoGEF. Indeed, we observed that PDZ-RhoGEF and LARG can form homo- and hetero-oligomers, whereas p115RhoGEF can only homo-oligomerize, and that this intermolecular interaction was mediated by their unique C-terminal regions. Deletion of the C-terminal tail of PDZ-RhoGEF had no significant effect on the GEF catalytic activity towards Rho in vitro, but resulted in a drastic increase in the ability to stimulate a serum response element reporter and the accumulation of the GTP-bound Rho in vivo. Furthermore, removal of the C-termini of each of the three RGL-containing GEFs unleashed their full transforming potential. Together, these findings suggest the existence of a novel mechanism controlling the activity of PDZ-RhoGEF, LARG, and p115RhoGEF, which involves homo- and hetero-oligomerization through their inhibitory C-terminal region.

Indexed as

Cell Transformation, NeoplasticAnimalsCell LineGuanine Nucleotide Exchange FactorsHumansMiceNIH 3T3 CellsPhosphorylationReceptors, GlutamateRho Guanine Nucleotide Exchange FactorsStructure-Activity RelationshipARHGEF11 protein, humanARHGEF12 protein, humanArhgef12 protein, mouseGuanine Nucleotide Exchange FactorsReceptors, GlutamateRho Guanine Nucleotide Exchange Factors

Identifiers

PMID14712228
OpenAlexW2032668695

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.