ArticleMolecular biology of the cell2007
Diacylglycerol kinase-alpha mediates hepatocyte growth factor-induced epithelial cell scatter by regulating Rac activation and membrane ruffling.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
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- Diacylglycerol Kinases: Shaping Diacylglycerol and Phosphatidic Acid Gradients to Control Cell Polarity.Frontiers in cell and developmental biology · 2016Review
- Regulation of Macropinocytosis by Diacylglycerol Kinase ζ.PloS one · 2015Article
- Physiological Signaling and Structure of the HGF Receptor MET.Biomedicines · 2014Review
- Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion.BMC cancer · 2014Article
- The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness.PloS one · 2014Article
- Identification of key signaling molecules involved in the activation of the swelling-activated chloride current in human glioblastoma cells.The Journal of membrane biology · 2014Article
- A potential role of progestin-induced laminin-5/α6-integrin signaling in the formation of side branches in the mammary gland.Endocrinology · 2012Article
- Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration.The Journal of cell biology · 2012Article
- Diacylglycerol kinase delta and protein kinase C(alpha) modulate epidermal growth factor receptor abundance and degradation through ubiquitin-specific protease 8.The Journal of biological chemistry · 2010Article
- Diacylglycerol kinase alpha mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Diacylglycerol kinases as sources of phosphatidic acid.Biochimica et biophysica acta · 2009Review
- Phosphatidic acid signaling regulation of Ras superfamily of small guanosine triphosphatases.Biochimica et biophysica acta · 2009Review
- Enzymatic measurement of phosphatidic acid in cultured cells.Journal of lipid research · 2009Article
- Mammalian diacylglycerol kinases: molecular interactions and biological functions of selected isoforms.Biochimica et biophysica acta · 2009Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diacylglycerol kinases (Dgk) phosphorylate diacylglycerol (DG) to phosphatidic acid (PA), thus turning off and on, respectively, DG-mediated and PA-mediated signaling pathways. We previously showed that hepatocyte growth factor (HGF), vascular endothelial growth factor, and anaplastic lymphoma kinase activate Dgkalpha in endothelial and leukemia cells through a Src-mediated mechanism and that activation of Dgkalpha is required for chemotactic, proliferative, and angiogenic signaling in vitro. Here, we investigate the downstream events and signaling pathways regulated by Dgkalpha, leading to cell scatter and migration upon HGF treatment and v-Src expression in epithelial cells. We report that specific inhibition of Dgkalpha, obtained either pharmacologically by R59949 treatment, or by expression of Dgkalpha dominant-negative mutant, or by small interfering RNA-mediated down-regulation of endogenous Dgkalpha, impairs 1) HGF- and v-Src-induced cell scatter and migration, without affecting the loss of intercellular adhesions; 2) HGF-induced cell spreading, lamellipodia formation, membrane ruffling, and focal adhesions remodeling; and 3) HGF-induced Rac activation and membrane targeting. In summary, we provide evidence that Dgkalpha, activated downstream of tyrosine kinase receptors and Src, regulates crucial steps directing Rac activation and Rac-dependent remodeling of actin cytoskeleton and focal contacts in migrating epithelial cells.
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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.