Evidence map›Paper›PMID 23467409›Full record

ArticleThe Journal of biological chemistry2013

PDZ-RhoGEF and LARG are essential for embryonic development and provide a link between thrombin and LPA receptors and Rho activation.

Constantinos M Mikelis, Todd R Palmby, May Simaan, Wenling Li, Roman Szabo, Ruth Lyons, Daniel Martin, Hiroshi Yagi, Shigetomo Fukuhara, Hiroki Chikumi and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

47 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Review
  3. GRespiratory research · 2024
    Review
  4. Review
  5. Oncogenic Gαq activates RhoJ through PDZ-RhoGEF.International journal of molecular sciences · 2023
    Article
  6. CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA.Arteriosclerosis, thrombosis, and vascular biology · 2023
    Article
  7. Endothelial-Specific Targeting of RhoA Signaling via CD31 Antibody-Conjugated Nanoparticles.The Journal of pharmacology and experimental therapeutics · 2023
    Article
  8. Article
  9. Article
  10. A network of GαScience signaling · 2022
    Article
  11. Article
  12. Article
  13. GαFrontiers in cell and developmental biology · 2022
    Review
  14. Review
  15. Review
  16. Low Dose of Penfluridol Inhibits VEGF-Induced Angiogenesis.International journal of molecular sciences · 2020
    Article
  17. Article
  18. Article
  19. Article
  20. Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018
    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

14 authors at 3 institutions in 1 country.

Constantinos M MikelisOral and Pharyngeal Cancer Branch, NIDCR, Genetics and Developmental Biology Center, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Todd R Palmby
May Simaan
Wenling Li
Roman Szabo
Ruth Lyons
Daniel Martin
Hiroshi Yagi
Shigetomo Fukuhara
Hiroki Chikumi
Rebeca Galisteo
Yoh-Suke Mukouyama
Thomas H Bugge
J Silvio Gutkind
National Institutes of Health · USNational Institute of Dental and Craniofacial Research · USNational Heart Lung and Blood Institute · US

Funding

Cell surface serine proteases in development, tissue repair, and malignancyZIADE000699 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI BUGGE, THOMAS H · 2009 to 2025
$34.1M
The study of stem cell and neuro-vascular developmentZIAHL005702 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MUKOUYAMA, YOH-SUKE · 2009 to 2025
$14.9M
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
Intramural NIH HHS Z01 DE000551
6 · The paper itself

Abstract

G protein-coupled receptors (GPCRs) linked to both members of the Gα12 family of heterotrimeric G proteins α subunits, Gα12 and Gα13, regulate the activation of Rho GTPases, thereby contributing to many key biological processes. Multiple Rho GEFs have been proposed to link Gα12/13 GPCRs to Rho activation, including PDZ-RhoGEF (PRG), leukemia-associated Rho GEF (LARG), p115-RhoGEF (p115), lymphoid blast crisis (Lbc), and Dbl. PRG, LARG, and p115 share the presence of a regulator of G protein signaling homology (RGS) domain. There is limited information on the biological roles of this RGS-containing family of RhoGEFs in vivo. p115-deficient mice are viable with some defects in the immune system and gastrointestinal motor dysfunctions, whereas in an initial study we showed that mice deficient for Larg are viable and resistant to salt-induced hypertension. Here, we generated knock-out mice for Prg and observed that these mice do not display any overt phenotype. However, deficiency in Prg and Larg leads to complex developmental defects and early embryonic lethality. Signaling from Gα11/q-linked GPCRs to Rho was not impaired in mouse embryonic fibroblasts defective in all three RGS-containing RhoGEFs. However, a combined lack of Prg, Larg, and p115 expression abolished signaling through Gα12/13 to Rho and thrombin-induced cell proliferation, directional migration, and nuclear signaling through JNK and p38. These findings provide evidence of an essential role for the RGS-containing RhoGEF family in signaling to Rho by Gα12/13-coupled GPCRs, which may likely play a critical role during embryonic development.

Indexed as

AnimalsCell LineCell MovementCell ProliferationEmbryo, MammalianEmbryonic DevelopmentFibroblastsGene Expression Regulation, DevelopmentalGTP-Binding Protein alpha Subunits, G12-G13GTP-Binding Protein alpha Subunits, Gq-G11Guanine Nucleotide Exchange FactorsHumansMiceMice, KnockoutReceptors, Lysophosphatidic AcidReceptors, ThrombinArhgef12 protein, mouseARHGEF1 protein, humanGTP-Binding Protein alpha Subunits, G12-G13GTP-Binding Protein alpha Subunits, Gq-G11Guanine Nucleotide Exchange FactorsReceptors, Lysophosphatidic AcidReceptors, Thrombinrho GTP-Binding ProteinsRho Guanine Nucleotide Exchange Factors

Identifiers

PMID23467409
PMCPMC3636907
OpenAlexW2041164953

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.