ArticlePloS one2015
Regulation of Macropinocytosis by Diacylglycerol Kinase ζ.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Mechanism of uptake and toxicity of a BCMA antibody drug conjugate with a MMAF payload by nonantigen expressing cells.Cell biology and toxicology · 2026Article
- PI Kinase-EhGEF2-EhRho5 axis contributes to LPA stimulated macropinocytosis in Entamoeba histolytica.PLoS pathogens · 2022Article
- Roles for 3' Phosphoinositides in Macropinocytosis.Sub-cellular biochemistry · 2022Article
- Macropinocytosis and Cancer: From Tumor Stress to Signaling Pathways.Sub-cellular biochemistry · 2022Review
- PI3Kβ is selectively required for growth factor-stimulated macropinocytosis.Journal of cell science · 2019Article
- A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells.Viruses · 2019Article
- Constitutive and stimulated macropinocytosis in macrophages: roles in immunity and in the pathogenesis of atherosclerosis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- Macropinocytosis, mTORC1 and cellular growth control.Cellular and molecular life sciences : CMLS · 2018Review
- DGKZ Acts as a Potential Oncogene in Osteosarcoma Proliferation Through Its Possible Interaction With ERK1/2 and MYC Pathway.Frontiers in oncology · 2018Article
- PKCα-mediated phosphorylation of the diacylglycerol kinase ζ MARCKS domain switches cell migration modes by regulating interactions with Rac1 and RhoA.The Journal of biological chemistryArticle
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Authors and funding
7 authors.
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Abstract
Macropinosomes arise from the closure of plasma membrane ruffles to bring about the non-selective uptake of nutrients and solutes into cells. The morphological changes underlying ruffle formation and macropinosome biogenesis are driven by actin cytoskeleton rearrangements under the control of the Rho GTPase Rac1. We showed previously that Rac1 is activated by diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid. Here, we show DGKζ is required for optimal macropinocytosis induced by growth factor stimulation of mouse embryonic fibroblasts. Time-lapse imaging of live cells and quantitative analysis revealed DGKζ was associated with membrane ruffles and nascent macropinosomes. Macropinocytosis was attenuated in DGKζ-null cells, as determined by live imaging and vaccinia virus uptake experiments. Moreover, macropinosomes that did form in DGKζ-null cells were smaller than those found in wild type cells. Rescue of this defect required DGKζ catalytic activity, consistent with it also being required for Rac1 activation. A constitutively membrane bound DGKζ mutant substantially increased the size of macropinosomes and potentiated the effect of a constitutively active Rac1 mutant on macropinocytosis. Collectively, our results suggest DGKζ functions in concert with Rac1 to regulate macropinocytosis.
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