ArticleThe Journal of biological chemistry2011
Evidence for two CRIB domains in phospholipase D2 (PLD2) that the enzyme uses to specifically bind to the small GTPase Rac2.
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 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Oleate activates PLD2 lipase and GEF activity by modulating membrane microdomain dynamics via S-acylation.Journal of lipid research · 2025Article
- Oleate Promotes Triple-Negative Breast Cancer Cell Migration by Enhancing Filopodia Formation through a PLD/Cdc42-Dependent Pathway.International journal of molecular sciences · 2024Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Coronin7 regulates WASP and SCAR through CRIB mediated interaction with Rac proteins.Scientific reports · 2015Article
- Two sites of action for PLD2 inhibitors: The enzyme catalytic center and an allosteric, phosphoinositide biding pocket.Biochimica et biophysica acta · 2015Article
- Mechanism of enzymatic reaction and protein-protein interactions of PLD from a 3D structural model.Cellular signalling · 2015Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis.The Journal of biological chemistry · 2014Review
- Role of phospholipase d in g-protein coupled receptor function.Membranes · 2014Article
- A Cdc42- and Rac-interactive binding (CRIB) domain mediates functions of coronin.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a human breast cancer xenograph model.Oncogene · 2013Article
- Macrophage migration arrest due to a winning balance of Rac2/Sp1 repression over β-catenin-induced PLD expression.Journal of leukocyte biology · 2013Article
- 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
- Increased cell growth due to a new lipase-GEF (Phospholipase D2) fastly acting on Ras.Cellular signalling · 2013Article
- Identification of the catalytic site of phospholipase D2 (PLD2) newly described guanine nucleotide exchange factor activity.The Journal of biological chemistry · 2012Article
- Biochemical and cellular implications of a dual lipase-GEF function of phospholipase D2 (PLD2).Journal of leukocyte biology · 2012Review
- Phospholipase D2 (PLD2) is a guanine nucleotide exchange factor (GEF) for the GTPase Rac2.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF).Cellular signalling · 2011Review
- Phospholipase D: enzymology, functionality, and chemical modulation.Chemical reviews · 2011Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Phospholipase D (PLD) and small GTPases are vital to cell signaling. We report that the Rac2 and the PLD2 isoforms exist in the cell as a lipase-GTPase complex that enables the two proteins to elicit their respective functionalities. A strong association between the two molecules was demonstrated by co-immunoprecipitation and was confirmed in living cells by FRET with CFP-Rac2 and YFP-PLD2 fluorescent chimeras. We have identified the amino acids in PLD2 that define a specific binding site to Rac2. This site is composed of two CRIB (Cdc42-and Rac-interactive binding) motifs that we have named "CRIB-1" and "CRIB-2" in and around the PH domain in PLD2. Deletion mutants PLD2-ΔCRIB-1/2 negate co-immunoprecipitation with Rac2 and diminish the FRET signal in living cells. The PLD2-Rac2 association was further confirmed in vitro using affinity-purified recombinant proteins. Binding was saturable with an apparent K(d) of 3 nm and was diminished with PLD2-ΔCRIB mutants. Furthermore, PLD2 bound more efficiently to Rac2-GTP than to Rac2-GDP or to a GDP-constitutive Rac2-N17 mutant. Increasing concentrations of recombinant Rac2 in vitro and in vivo during cell adhesion inhibit PLD2. Conversely, Rac2 activity is increased in the presence of PLD2-WT but not in PLD2-ΔCRIB. We propose that in activated cells PLD2 affects Rac2 in an initial positive feedback, but as Rac2-GTP accumulates in the cell, this constitutes a "termination signal" leading to PLD2 inactivation.
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