Evidence map›Paper›PMID 21878635›Full record

ArticleThe Journal of biological chemistry2011

Group X secreted phospholipase A2 proenzyme is matured by a furin-like proprotein convertase and releases arachidonic acid inside of human HEK293 cells.

Ikram Jemel, Hiromi Ii, Rob C Oslund, Christine Payré, Anne-Sophie Dabert-Gay, Dominique Douguet, Khaoula Chargui, Sabine Scarzello, Michael H Gelb, Gérard Lambeau

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

22 citing papers in PubMed, 35 citations in OpenAlex.

  1. Phospholipases: Where Do We Stand?Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. sPLAScience advances · 2026
    Article
  3. Intestinal overexpression ofFrontiers in cellular and infection microbiology · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Updating Phospholipase ABiomolecules · 2020
    Review
  8. Article
  9. Secreted Phospholipase AJournal of immunology (Baltimore, Md. : 1950) · 2020
    Article
  10. Function of secreted phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019
    Review
  11. Article
  12. Lipoquality control by phospholipase AProceedings of the Japan Academy. Series B, Physical and biological sciences · 2017
    Review
  13. The Roles of the Secreted Phospholipase AAdvances in immunology · 2016
    Review
  14. Article
  15. A new era of secreted phospholipase A₂.Journal of lipid research · 2015
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

10 authors at 2 institutions in 1 country.

Ikram JemelInstitut de Pharmacologie Moléculaire et Cellulaire, UMR6097, CNRS et Université de Nice-Sophia-Antipolis, 660 Route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Hiromi Ii
Rob C Oslund
Christine Payré
Anne-Sophie Dabert-Gay
Dominique Douguet
Khaoula Chargui
Sabine Scarzello
Michael H Gelb
Gérard Lambeau
Institut de Pharmacologie Moléculaire et Cellulaire · FRCentre National de la Recherche Scientifique · FR

Funding

Biochemical Studies of 14-kDa Phospholipases A2R37HL036235 · NHLBI · UNIVERSITY OF WASHINGTON · PI GELB, MICHAEL H · 2007 to 2016
$4.1M
NHLBI NIH HHS R37 HL036235NHLBI NIH HHS R37HL36235
6 · The paper itself

Abstract

Among mammalian secreted phospholipases A(2) (sPLA(2)s), group X sPLA(2) has the most potent hydrolyzing activity toward phosphatidylcholine and is involved in arachidonic acid (AA) release. Group X sPLA(2) is produced as a proenzyme and contains a short propeptide of 11 amino acids ending with a dibasic motif, suggesting cleavage by proprotein convertases. Although the removal of this propeptide is clearly required for enzymatic activity, the cellular location and the protease(s) involved in proenzyme conversion are unknown. Here we have analyzed the maturation of group X sPLA(2) in HEK293 cells, which have been extensively used to analyze sPLA(2)-induced AA release. Using recombinant mouse (PromGX) and human (ProhGX) proenzymes; HEK293 cells transfected with cDNAs coding for full-length ProhGX, PromGX, and propeptide mutants; and various permeable and non-permeable sPLA(2) inhibitors and protease inhibitors, we demonstrate that group X sPLA(2) is mainly converted intracellularly and releases AA before externalization from the cell. Most strikingly, the exogenous proenzyme does not elicit AA release, whereas the transfected proenzyme does elicit AA release in a way insensitive to non-permeable sPLA(2) inhibitors. In transfected cells, a permeable proprotein convertase inhibitor, but not a non-permeable one, prevents group X sPLA(2) maturation and partially blocks AA release. Mutations at the dibasic motif of the propeptide indicate that the last basic residue is required and sufficient for efficient maturation and AA release. All together, these results argue for the intracellular maturation of group X proenzyme in HEK293 cells by a furin-like proprotein convertase, leading to intracellular release of AA during secretion.

Indexed as

Amino Acid MotifsAnimalsArachidonic AcidEnzyme PrecursorsGroup X Phospholipases A2HEK293 CellsHumansMiceMutationProprotein ConvertasesProtease InhibitorsArachidonic AcidEnzyme PrecursorsGroup X Phospholipases A2Proprotein ConvertasesProtease Inhibitors

Identifiers

PMID21878635
PMCPMC3196088
OpenAlexW2093654338

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.