ArticleProceedings of the National Academy of Sciences of the United States of America2011
Phospholipase D2 (PLD2) is a guanine nucleotide exchange factor (GEF) for the GTPase Rac2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Oleate activates PLD2 lipase and GEF activity by modulating membrane microdomain dynamics via S-acylation.Journal of lipid research · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Oleate Promotes Triple-Negative Breast Cancer Cell Migration by Enhancing Filopodia Formation through a PLD/Cdc42-Dependent Pathway.International journal of molecular sciences · 2024Article
- Oncostatin M Reduces Pathological Neovascularization in the Retina Through Müller Cell Activation.Investigative ophthalmology & visual science · 2024Article
- Phospholipase D2 is a positive regulator of sirtuin 1 and modulates p53-mediated apoptosis via sirtuin 1.Experimental & molecular medicine · 2021Article
- D-series Resolvins activate Phospholipase D in phagocytes during inflammation and resolution.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Phospholipase D2 in prostate cancer: protein expression changes with Gleason score.British journal of cancer · 2019Article
- Phosphatidic acid generated by PLD2 promotes the plasma membrane recruitment of IQGAP1 and neointima formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Tumor cell-secreted PLD increases tumor stemness by senescence-mediated communication with microenvironment.Oncogene · 2019Article
- Phospholipase D and phosphatidic acid in the biogenesis and cargo loading of extracellular vesicles.Journal of lipid research · 2018Review
- Phospholipase D isoforms differentially regulate leukocyte responses to acute lung injury.Journal of leukocyte biology · 2018Article
- Proliferative and metastatic roles for Phospholipase D in mouse models of cancer.Advances in biological regulation · 2018Review
- A module for Rac temporal signal integration revealed with optogenetics.The Journal of cell biology · 2017Article
- A Phosphatidic Acid (PA) conveyor system of continuous intracellular transport from cell membrane to nucleus maintains EGF receptor homeostasis.Oncotarget · 2016Article
- Blockade of PLD2 Ameliorates Intestinal Mucosal Inflammation of Inflammatory Bowel Disease.Mediators of inflammation · 2016Article
- Phosphatidic Acid (PA) can Displace PPARα/LXRα Binding to The EGFR Promoter Causing its Transrepression in Luminal Cancer Cells.Scientific reports · 2015Article
- Mechanism of enzymatic reaction and protein-protein interactions of PLD from a 3D structural model.Cellular signalling · 2015Article
- A river runs through it: how autophagy, senescence, and phagocytosis could be linked to phospholipase D by Wnt signaling.Journal of leukocyte biology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We have discovered that the enzyme phospholipase D2 (PLD2) binds directly to the small GTPase Rac2, resulting in PLD2 functioning as a guanine nucleotide exchange factor (GEF), because it switches Rac2 from the GDP-bound to the GTP-bound states. This effect is large enough to be meaningful (∼72% decrease for GDP dissociation and 300% increase for GTP association, both with PLD2), it has a half-time of ∼7 min, is enhanced with increasing PLD2 concentrations, and compares favorably with other known GEFs, such as Vav-1. The PLD2-Rac2 protein-protein interaction is sufficient for the GEF function, because it can be demonstrated in vitro with just recombinant proteins without lipid substrates, and a catalytically inactive lipase (PLD2-K758R) has GEF activity. Apart from this function, exogenous phosphatidic acid by itself (300 pM) increases GTP binding and enhances PLD2-K758R-mediated GTP binding (by ∼34%) but not GDP dissociation. Regarding the PLD2-Rac2 protein-protein association, it involves, for PLD2, residues 263-266 within a Cdc42/Rac interactive binding region in the PH domain, as well as the PX domain, and it involves, for Rac2, residue N17 within its Switch-1 region. PLD2's GEF function is demonstrated in living cells, because silencing PLD2 results in reduced Rac2 activity, whereas PLD2-initiated Rac2 activation enhances cell adhesion, chemotaxis, and phagocytosis. There are several known GEFs, but we report that this GEF is harbored in a phospholipase. The benefit to the cell is that PLD2 brings spatially separated molecules together in a membrane environment, ready for fast intracellular signaling and cell function.
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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.