ArticleMolecular and cellular biology2011
The dual effect of Rac2 on phospholipase D2 regulation that explains both the onset and termination of chemotaxis.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Overexpression of Ras-Related C3 Botulinum Toxin Substrate 2 Radiosensitizes Melanoma CellsOxidative medicine and cellular longevity · 2019Article
- Article
- 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
- CSF-1 receptor signaling in myeloid cells.Cold Spring Harbor perspectives in biology · 2014Review
- Phosphatidic acid, phospholipase D and tumorigenesis.Advances in biological regulation · 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
- Friedreich's ataxia, frataxin, PIP5K1B: echo of a distant fracas.Oxidative medicine and cellular longevity · 2013Review
- 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
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
We document a biphasic effect of Rac2 on the activation and inhibition of PLD2. Cells overexpressing Rac2 and PLD2 simultaneously show a robust initial (<10 min) response toward a chemoattractant that is later (>30 min) greatly diminished over PLD2-only controls. The first phase is due to the presence of a Rac2-PLD2 positive-feedback loop. To explain the mechanism for the Rac2-led PLD2 inhibition (the second phase), we used leukocytes from wild-type (WT) and Rac2(-/-) knockout mice. Rac2(-/-) cells displayed an enhanced PLD2 (but not PLD1) enzymatic activity, confirming the inhibitory role of Rac2. Late inhibitory responses on PLD2 due to Rac2 were reversed in the presence of phosphatidylinositol 4,5-bisphosphate (PIP(2)) both in vitro (purified GST-PH-PLD2, where GST is glutathione S-transferase and PH is pleckstrin homology) and in vivo. Coimmunoprecipitation and immunofluorescence microscopy indicated that PLD2 and Rac2 remain together. The presence of an "arc" of Rac2 at the leading edge of leukocyte pseudopodia and PLD2 physically posterior to this wave of Rac2 was observed in late chemotaxis. We propose Rac-led inhibition of PLD2 function is due to sterical interference of Rac with PLD2's PH binding site to the membrane and deprivation of the PIP(2). This work supports the importance of functional interactions between PLD and Rac in the biological response of cell migration.
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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.