Evidence map›Paper›PMID 22740689›Full record

ArticleThe Journal of biological chemistry2012

A Salmonella typhimurium-translocated glycerophospholipid:cholesterol acyltransferase promotes virulence by binding to the RhoA protein switch regions.

Doris L LaRock, Peter S Brzovic, Itay Levin, Marie-Pierre Blanc, Samuel I Miller

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

18 citing papers in PubMed, 32 citations in OpenAlex.

  1. Molecular biology of the cell · 2025
    Article
  2. Speaking the host language: howMicrobiology (Reading, England) · 2023
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. What the SIF Is Happening-The Role of IntracellularFrontiers in cellular and infection microbiology · 2017
    Review
  13. Article
  14. Bacterial Sphingomyelinases and Phospholipases as Virulence Factors.Microbiology and molecular biology reviews : MMBR · 2016
    Review
  15. Targeting of the hydrophobic metabolome by pathogens.Traffic (Copenhagen, Denmark) · 2015
    Review
  16. Salmonellae interactions with host processes.Nature reviews. Microbiology · 2015
    Review
  17. Structural basis for the recruitment and activation of the Legionella phospholipase VipD by the host GTPase Rab5.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  18. 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

5 authors at 1 institution in 1 country.

Doris L LaRockDepartment of Microbiology, University of Washington, Seattle, WA 98195, USA.
Peter S Brzovic
Itay Levin
Marie-Pierre Blanc
Samuel I Miller
University of Washington · US

Funding

Variation in Human Innate ImmunityU54AI057141 · NIAID · UNIVERSITY OF WASHINGTON · PI COOKSON, BRAD T · 2003 to 2013
$102.3M
TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
SALMONELLA PATHOGENICITY ISLAND 2 EFFECTOR PROTEINSR01AI048683 · NIAID · UNIVERSITY OF WASHINGTON · PI MILLER, SAMUEL I · 2001 to 2015
$5.1M
NIAID NIH HHS R01 AI048683NIAID NIH HHS U54 AI057141NIGMS NIH HHS T32 GM07270
6 · The paper itself

Abstract

Salmonella enterica serovar typhimurium translocates a glycerophospholipid:cholesterol acyltransferase (SseJ) into the host cytosol after its entry into mammalian cells. SseJ is recruited to the cytoplasmic face of the host cell phagosome membrane where it is activated upon binding the small GTPase, RhoA. SseJ is regulated similarly to cognate eukaryotic effectors, as only the GTP-bound form of RhoA family members stimulates enzymatic activity. Using NMR and biochemistry, this work demonstrates that SseJ competes effectively with Rhotekin, ROCK, and PKN1 in binding to a similar RhoA surface. The RhoA surface that binds SseJ includes the regulatory switch regions that control activation of mammalian effectors. These data were used to create RhoA mutants with altered SseJ binding and activation. This structure-function analysis supports a model in which SseJ activation occurs predominantly through binding to residues within switch region II. We further defined the nature of the interaction between SseJ and RhoA by constructing SseJ mutants in the RhoA binding surface. These data indicate that SseJ binding to RhoA is required for recruitment of SseJ to the endosomal network and for full Salmonella virulence for inbred susceptible mice, indicating that regulation of SseJ by small GTPases is an important virulence strategy of this bacterial pathogen. The dependence of a bacterial effector on regulation by a mammalian GTPase defines further how intimately host pathogen interactions have coevolved through similar and divergent evolutionary strategies.

Indexed as

AcyltransferasesAnimalsApoptosis Regulatory ProteinsBacterial ProteinsGTP-Binding ProteinsHeLa CellsHumansIntracellular Signaling Peptides and ProteinsMiceMutationNuclear Magnetic Resonance, BiomolecularProtein BindingProtein Kinase CProtein Structure, TertiaryrhoA GTP-Binding Proteinrho GTP-Binding ProteinsAcyltransferasesApoptosis Regulatory ProteinsBacterial Proteinsglycerophospholipid-cholesterol acyltransferaseGTP-Binding ProteinsIntracellular Signaling Peptides and ProteinsProtein Kinase Cprotein kinase NrhoA GTP-Binding ProteinRHOA protein, humanRhoA protein, mouserho GTP-Binding ProteinsRTKN protein, humanRtkn protein, mouseVirulence Factors

Identifiers

PMID22740689
PMCPMC3436183
OpenAlexW2022556760

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.