ArticleProceedings of the National Academy of Sciences of the United States of America2010
Diacylglycerol kinase alpha mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 64 citations in OpenAlex.
- Modulators of Diacylglycerol Kinase Activity: A Review of Advances and Challenges.Medicinal research reviews · 2026Review
- Nuclear Mechanotransduction at the Crossroads: How Membrane Receptors Remodel the Perinuclear Cytoskeleton to Drive Cancer and Disease.International journal of biological sciences · 2026Review
- DGKs in lipid signaling and disease intervention: structural basis, pathological mechanisms, and emerging therapeutic strategies.Cellular & molecular biology letters · 2025Review
- Aberrant MET activation impairs perinuclear actin cap organization with YAP1 cytosolic relocation.Communications biology · 2023Article
- Crosstalk between diacylglycerol kinase and protein kinase A in the regulation of airway smooth muscle cell proliferation.Respiratory research · 2023Article
- Review
- Underappreciated roles for Rho GDP dissociation inhibitors (RhoGDIs) in cell function: Lessons learned from the pancreatic islet β-cell.Biochemical pharmacology · 2022Review
- Autocrine regulation of airway smooth muscle contraction by diacylglycerol kinase.Journal of cellular physiology · 2022Article
- Therapeutic Targeting of DGKA-Mediated Macropinocytosis Leads to Phospholipid Reprogramming in Tuberous Sclerosis Complex.Cancer research · 2021Article
- Identification of Key Phospholipids That Bind and Activate Atypical PKCs.Biomedicines · 2021Article
- Interplay Between SNX27 and DAG Metabolism in the Control of Trafficking and Signaling at the IS.International journal of molecular sciences · 2020Review
- Diacylglycerol Kinase Alpha in Radiation-Induced Fibrosis: Potential as a Predictive Marker or Therapeutic Target.Frontiers in oncology · 2020Review
- Review
- The Volume-Regulated Anion Channel in Glioblastoma.Cancers · 2019Review
- A Salutary Role of Reactive Oxygen Species in Intercellular Tunnel-Mediated Communication.Frontiers in cell and developmental biology · 2018Review
- Review
- Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis.Nature communications · 2016Article
- Endosomal Na+/H+ exchanger NHE5 influences MET recycling and cell migration.Molecular biology of the cell · 2016Article
- Article
- Diacylglycerol Kinases: Shaping Diacylglycerol and Phosphatidic Acid Gradients to Control Cell Polarity.Frontiers in cell and developmental biology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diacylglycerol kinases (DGKs) convert diacylglycerol (DAG) into phosphatidic acid (PA), acting as molecular switches between DAG- and PA-mediated signaling. We previously showed that Src-dependent activation and plasma membrane recruitment of DGKalpha are required for growth-factor-induced cell migration and ruffling, through the control of Rac small-GTPase activation and plasma membrane localization. Herein we unveil a signaling pathway through which DGKalpha coordinates the localization of Rac. We show that upon hepatocyte growth-factor stimulation, DGKalpha, by producing PA, provides a key signal to recruit atypical PKCzeta/iota (aPKCzeta/iota) in complex with RhoGDI and Rac at ruffling sites of colony-growing epithelial cells. Then, DGKalpha-dependent activation of aPKCzeta/iota mediates the release of Rac from the inhibitory complex with RhoGDI, allowing its activation and leading to formation of membrane ruffles, which constitute essential requirements for cell migration. These findings highlight DGKalpha as the central element of a lipid signaling pathway linking tyrosine kinase growth-factor receptors to regulation of aPKCs and RhoGDI, and providing a positional signal regulating Rac association to the plasma membrane.
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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 Socratic graph.