ArticleMolecular biology of the cell2009
Diacylglycerol kinase zeta regulates actin cytoskeleton reorganization through dissociation of Rac1 from RhoGDI.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 77 citations in OpenAlex.
- Lipidomic profiling of endometrial cancer using desorption electrospray ionization mass spectrometry imaging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ERK3 and DGKζ interact to modulate cell motility in lung cancer cells.Frontiers in cell and developmental biology · 2023Article
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- Underappreciated roles for Rho GDP dissociation inhibitors (RhoGDIs) in cell function: Lessons learned from the pancreatic islet β-cell.Biochemical pharmacology · 2022Review
- Actin Modulation Regulates the Alpha-1-Syntrophin/p66Shc Mediated Redox Signaling Contributing to the RhoA GTPase Protein Activation in Breast Cancer Cells.Frontiers in oncology · 2022Article
- Ion Channels in Glioma Malignancy.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.European journal of immunology · 2020Article
- Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases.International journal of molecular sciences · 2020Review
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
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- The role of mitochondrial dynamics in human cancers.American journal of cancer research · 2020Review
- Diacylglycerol Kinase Alpha in Radiation-Induced Fibrosis: Potential as a Predictive Marker or Therapeutic Target.Frontiers in oncology · 2020Review
- Review
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- The Volume-Regulated Anion Channel in Glioblastoma.Cancers · 2019Review
- A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells.Viruses · 2019Article
- FRET biosensor allows spatio-temporal observation of shear stress-induced polar RhoGDIα activation.Communications biology · 2018Article
- Every day I'm rufflin': Calcium sensing and actin dynamics in the growth factor-independent membrane ruffling of professional phagocytes.Small GTPases · 2017Review
- Mitochondrial lipids in neurodegeneration.Cell and tissue research · 2017Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Activation of Rac1 GTPase signaling is stimulated by phosphorylation and release of RhoGDI by the effector p21-activated kinase 1 (PAK1), but it is unclear what initiates this potential feed-forward mechanism for regulation of Rac activity. Phosphatidic acid (PA), which is produced from the lipid second messenger diacylglycerol (DAG) by the action of DAG kinases (DGKs), is known to activate PAK1. Here, we investigated whether PA produced by DGKzeta initiates RhoGDI release and Rac1 activation. In DGKzeta-deficient fibroblasts PAK1 phosphorylation and Rac1-RhoGDI dissociation were attenuated, leading to reduced Rac1 activation after platelet-derived growth factor stimulation. The cells were defective in Rac1-regulated behaviors, including lamellipodia formation, membrane ruffling, migration, and spreading. Wild-type DGKzeta, but not a kinase-dead mutant, or addition of exogenous PA rescued Rac activation. DGKzeta stably associated with PAK1 and RhoGDI, suggesting these proteins form a complex that functions as a Rac1-selective RhoGDI dissociation factor. These results define a pathway that links diacylglycerol, DGKzeta, and PA to the activation of Rac1: the PA generated by DGKzeta activates PAK1, which dissociates RhoGDI from Rac1 leading to changes in actin dynamics that facilitate the changes necessary for cell motility.
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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.