ArticleThe Journal of biological chemistry2012
Identification of the catalytic site of phospholipase D2 (PLD2) newly described guanine nucleotide exchange factor activity.
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 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Ras GEF Mouse Models for the Analysis of Ras Biology and Signaling.Methods in molecular biology (Clifton, N.J.) · 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
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Tumor cell-secreted PLD increases tumor stemness by senescence-mediated communication with microenvironment.Oncogene · 2019Article
- Functional regulation of plant NADPH oxidase and its role in signaling.Plant signaling & behavior · 2017Review
- PLD2 regulates microtubule stability and spindle migration in mouse oocytes during meiotic division.PeerJ · 2017Article
- Phospholipase D2 promotes degradation of hypoxia-inducible factor-1α independent of lipase activity.Experimental & molecular medicine · 2015Article
- Phosphatidic Acid Increases Epidermal Growth Factor Receptor Expression by Stabilizing mRNA Decay and by Inhibiting Lysosomal and Proteasomal Degradation of the Internalized Receptor.Molecular and cellular biology · 2015Article
- Mechanism of enzymatic reaction and protein-protein interactions of PLD from a 3D structural model.Cellular signalling · 2015Article
- Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis.The Journal of biological chemistry · 2014Review
- Jak3 enables chemokine-dependent actin cytoskeleton reorganization by regulating cofilin and Rac/Rhoa GTPases activation.PloS one · 2014Article
- A GEF-to-phospholipase molecular switch caused by phosphatidic acid, Rac and JAK tyrosine kinase that explains leukocyte cell migration.Journal of cell science · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have demonstrated that phospholipase D2 (PLD2) is a guanine nucleotide exchange factor (GEF) for Rac2 and determined the PLD2 domains and amino acid site(s) responsible for its GEF activity. Experiments using GST fusion proteins or GST-free counterparts, purified proteins revealed that the PX domain is sufficient to exert GEF activity similar to full-length PLD2. The PLD2-GEF catalytic site is formed by a hydrophobic pocket of residues Phe-107, Phe-129, Leu-166, and Leu-173, all of which are in the PX domain. A nearby Arg-172 is also important in the overall activity. PX mutants altering any of those five amino acids fail to have GEF activity but still bind to Rac2, while their lipase activity was mostly unaffected. In addition to the PX domain, a region in the pleckstrin homology domain (Ile-306-Ala-310) aids in the PX-mediated GEF activity by providing a docking site to hold Rac2 in place during catalysis. We conclude that PLD2 is a unique GEF, with the PX being the major catalytic domain for its GEF activity, whereas the pleckstrin homology domain assists in the PX-mediated activity. The physiological relevance of this novel GEF in cell biology is demonstrated here in chemotaxis and phagocytosis of leukocytes, as the specific PX and PH mutants abolished cell function. Thus, this study reveals for the first time the catalytic site that forms the basis for the mechanism behind the GEF activity of PLD2.
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