Evidence map›Paper›PMID 37239919›Full record

ArticleInternational journal of molecular sciences2023

Mutations in the Vicinity of the IRAK3 Guanylate Cyclase Center Impact Its Subcellular Localization and Ability to Modulate Inflammatory Signaling in Immortalized Cell Lines.

Ilona Turek, Trang H Nguyen, Charles Galea, Isaiah Abad, Lubna Freihat, David T Manallack, Tony Velkov, Helen Irving

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Role of TLRs as signaling cascades to combat infectious diseases: a review.Cellular and molecular life sciences : CMLS · 2025
    Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. The discovery of hidden guanylate cyclases (GCs) in theComputational and structural biotechnology journal · 2023
    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

8 authors at 2 institutions in 1 country.

Ilona TurekDepartment of Rural Clinical Sciences, La Trobe Rural Health School, La Trobe University, Bendigo, VIC 3552, Australia.ORCID 0000-0001-6457-7456
Trang H NguyenDepartment of Rural Clinical Sciences, La Trobe Rural Health School, La Trobe University, Bendigo, VIC 3552, Australia.
Charles GaleaMonash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
Isaiah AbadMonash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
Lubna FreihatMonash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
David T ManallackMonash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
Tony VelkovDepartment of Microbiology, Monash University, Wellington Rd, Clayton, VIC 3800, Australia.ORCID 0000-0002-0017-7952
Helen IrvingDepartment of Rural Clinical Sciences, La Trobe Rural Health School, La Trobe University, Bendigo, VIC 3552, Australia.ORCID 0000-0002-1514-0909
Monash University · AULa Trobe University · AU

Funding

La Trobe University Understanding Disease Research Focus Area 2020-xUnited States Army Research Office W911NF-17-1-0303United States Army Research Office W911NF-19-1-0435
6 · The paper itself

Abstract

Interleukin-1 receptor-associated kinase 3 (IRAK3) modulates the magnitude of cellular responses to ligands perceived by interleukin-1 receptors (IL-1Rs) and Toll-like receptors (TLRs), leading to decreases in pro-inflammatory cytokines and suppressed inflammation. The molecular mechanism of IRAK3's action remains unknown. IRAK3 functions as a guanylate cyclase, and its cGMP product suppresses lipopolysaccharide (LPS)-induced nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) activity. To understand the implications of this phenomenon, we expanded the structure-function analyses of IRAK3 through site-directed mutagenesis of amino acids known or predicted to impact different activities of IRAK3. We verified the capacity of the mutated IRAK3 variants to generate cGMP in vitro and revealed residues in and in the vicinity of its GC catalytic center that impact the LPS-induced NFκB activity in immortalized cell lines in the absence or presence of an exogenous membrane-permeable cGMP analog. Mutant IRAK3 variants with reduced cGMP generating capacity and differential regulation of NFκB activity influence subcellular localization of IRAK3 in HEK293T cells and fail to rescue IRAK3 function in

Indexed as

Guanylate CyclaseInterleukin-1 Receptor-Associated KinasesHEK293 CellsHumansLipopolysaccharidesMutationNF-kappa BGuanylate CyclaseInterleukin-1 Receptor-Associated KinasesIRAK3 protein, humanLipopolysaccharidesNF-kappa Bcyclic guanosine monophosphate (cGMP)guanylate cyclasehuman Toll-like receptor 4 (hTLR4)inflammatory cytokinesinterleukin-1 receptor-associated kinase 3 (IRAK3 or IRAK-M)lipopolysaccharidenuclear factor kappa-light-chain-enhancer of activated B (NFκB)

Identifiers

PMID37239919
PMCPMC10217915
OpenAlexW4376138417

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.