ArticleMolecular biology of the cell2008
Phospholipase D activity regulates integrin-mediated cell spreading and migration by inducing GTP-Rac translocation to the plasma membrane.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 91 citations in OpenAlex.
- Small Extracellular Vesicle and Total Lipid Profiles Provide a Diagnostic Advantage Over CA-125 Across Ovarian Cancer Subtypes.Journal of extracellular vesicles · 2026Article
- Clinical Significance of Combined Epithelial-Mesenchymal Transition Markers Expression and Role of Rac1 in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Upregulated phospholipase D2 expression and activity is related to the metastatic properties of melanoma.Oncology letters · 2022Article
- New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein.International journal of molecular sciences · 2020Review
- The first DEP domain of the RhoGEF P-Rex1 autoinhibits activity and contributes to membrane binding.The Journal of biological chemistry · 2020Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation.Scientific reports · 2019Article
- Phosphatidic Acid: From Pleiotropic Functions to Neuronal Pathology.Frontiers in cellular neuroscience · 2019Review
- RAC1-GTP promotes epithelial-mesenchymal transition and invasion of colorectal cancer by activation of STAT3.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Distinctive roles of Rac1 and Rab29 in LRRK2 mediated membrane trafficking and neurite outgrowth.Journal of biomedical research · 2018Article
- Phospholipase D is Dispensable for Epidermal Growth Factor-Induced Chemotaxis.The Kobe journal of medical sciences · 2017Article
- Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin.Scientific reports · 2017Article
- Differential Roles of Phospholipase D Proteins in FcεRI-Mediated Signaling and Mast Cell Function.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- ADP-ribosylation factor 6 (ARF6) bidirectionally regulates dendritic spine formation depending on neuronal maturation and activity.The Journal of biological chemistry · 2015Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- The role of phospholipase D1 in liver fibrosis induced by dimethylnitrosamine in vivo.Digestive diseases and sciences · 2014Article
- EDI3 links choline metabolism to integrin expression, cell adhesion and spreading.Cell adhesion & migration · 2014Article
- Liposome reconstitution and modulation of recombinant prenylated human Rac1 by GEFs, GDI1 and Pak1.PloS one · 2014Article
- Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury.American journal of respiratory cell and molecular biology · 2013Review
- Aberrant lipid metabolism: an emerging diagnostic and therapeutic target in ovarian cancer.International journal of molecular sciences · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small GTPase Rac is a crucial regulator of actin cytoskeletal rearrangement, and it plays an important role in cell spreading, migration, mitogenesis, phagocytosis, superoxide generation, and axonal growth. It is generally accepted that Rac activity is regulated by the guanosine triphosphate (GTP)/guanosine diphosphate (GDP) cycle. But, it is suggested that in addition to Rac-GTP loading, membrane localization is required for the initiation of downstream effector signaling. However, the molecular mechanisms that control the targeting of GTP-Rac to the plasma membrane remain largely unknown. Here, we have uncovered a signaling pathway linking phospholipase D (PLD) to the localized functions of Rac1. We show that PLD product phosphatidic acid (PA) acts as a membrane anchor of Rac1. The C-terminal polybasic motif of Rac1 is responsible for direct interaction with PA, and Rac1 mutated in this region is incapable of translocating to the plasma membrane and of activating downstream target p21-activated kinase upon integrin activation. Finally, we show that PA induces dissociation of Rho-guanine nucleotide dissociation inhibitor from Rac1 and that PA-mediated Rac1 localization is important for integrin-mediated lamellipodia formation, cell spreading, and migration. These results provide a novel molecular mechanism for the GTP-Rac1 localization through the elevating PLD activity, and they suggest a general mechanism for diverse cellular functions that is required localized Rac activation.
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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.