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.
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.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Phospholipases: Where Do We Stand?Methods in molecular biology (Clifton, N.J.) · 2027Review
- sPLAScience advances · 2026Article
- Intestinal overexpression ofFrontiers in cellular and infection microbiology · 2025Article
- Interplay between C1-inhibitor and group IIA secreted phospholipase AImmunologic research · 2023Article
- Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase AFrontiers in cell and developmental biology · 2022Article
- What do secreted phospholipases ABiochimie · 2021Review
- Updating Phospholipase ABiomolecules · 2020Review
- Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment.International journal of environmental research and public health · 2020Article
- Secreted Phospholipase AJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Function of secreted phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- The dual role of group V secretory phospholipase AEndocrine · 2017Article
- Lipoquality control by phospholipase AProceedings of the Japan Academy. Series B, Physical and biological sciences · 2017Review
- The Roles of the Secreted Phospholipase AAdvances in immunology · 2016Review
- Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils.The Journal of allergy and clinical immunology · 2016Article
- A new era of secreted phospholipase A₂.Journal of lipid research · 2015Article
- In vitro anti-Plasmodium falciparum properties of the full set of human secreted phospholipases A2.Infection and immunity · 2015Article
- Ectopically expressed pro-group X secretory phospholipase A2 is proteolytically activated in mouse adrenal cells by furin-like proprotein convertases: implications for the regulation of adrenal steroidogenesis.The Journal of biological chemistry · 2015Article
- Group X secretory phospholipase A2 regulates insulin secretion through a cyclooxygenase-2-dependent mechanism.The Journal of biological chemistry · 2014Article
- Secretory phospholipase A2 enzymes as pharmacological targets for treatment of disease.Biochemical pharmacology · 2014Review
- Group X secreted phospholipase A(2) induces lipid droplet formation and prolongs breast cancer cell survival.Molecular cancer · 2013Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
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.