ArticleThe Journal of biological chemistry2009
Phospholipase D-mediated activation of IQGAP1 through Rac1 regulates hyperoxia-induced p47phox translocation and reactive oxygen species generation in lung endothelial cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 65 citations in OpenAlex.
- IQGAP1 participates in bone marrow-derived macrophage recruitment and involves in liver inflammation/fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Article
- The scaffold protein IQGAP1 promotes reorientation of epithelial cell polarity at the two-cell stage for cystogenesis.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Tight junction protein cingulin variant is associated with cancer susceptibility by overexpressed IQGAP1 and Rac1-dependent epithelial-mesenchymal transition.Journal of experimental & clinical cancer research : CR · 2024Article
- Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.Antioxidants (Basel, Switzerland) · 2023Review
- CDC42-IQGAP Interactions Scrutinized: New Insights into the Binding Properties of the GAP-Related Domain.International journal of molecular sciences · 2022Article
- CD200R1L is a functional evolutionary conserved activating receptor in human neutrophils.Journal of leukocyte biology · 2022Article
- PLD1 promotes reactive oxygen species production in vascular smooth muscle cells and injury-induced neointima formation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- Selectivity Determinants of RHO GTPase Binding to IQGAPs.International journal of molecular sciences · 2021Article
- Renal Dopamine Receptors and Oxidative Stress: Role in Hypertension.Antioxidants & redox signaling · 2021Review
- Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function.The Journal of biological chemistry · 2020Article
- D-series Resolvins activate Phospholipase D in phagocytes during inflammation and resolution.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways.International journal of molecular sciences · 2020Review
- Endothelial IQGAP1 regulates leukocyte transmigration by directing the LBRC to the site of diapedesis.The Journal of experimental medicine · 2019Article
- Role of phospholipase D in bleomycin-induced mitochondrial reactive oxygen species generation, mitochondrial DNA damage, and pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Endogenous IQGAP1 and IQGAP3 do not functionally interact with Ras.Scientific reports · 2019Article
- Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function.Current topics in membranes · 2018Article
- IQGAP1 Interaction with RHO Family Proteins Revisited: KINETIC AND EQUILIBRIUM EVIDENCE FOR MULTIPLE DISTINCT BINDING SITES.The Journal of biological chemistry · 2016Article
- Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Bimodal role of NADPH oxidases in the regulation of biglycan-triggered IL-1β synthesis.Matrix biology : journal of the International Society for Matrix Biology · 2016Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Phosphatidic acid generated by the activation of phospholipase D (PLD) functions as a second messenger and plays a vital role in cell signaling. Here we demonstrate that PLD-dependent generation of phosphatidic acid is critical for Rac1/IQGAP1 signal transduction, translocation of p47(phox) to cell periphery, and ROS production. Exposure of [(32)P]orthophosphate-labeled human pulmonary artery endothelial cells (HPAECs) to hyperoxia (95% O(2) and 5% CO(2)) in the presence of 0.05% 1-butanol, but not tertiary-butanol, stimulated PLD as evidenced by accumulation of [(32)P]phosphatidylbutanol. Infection of HPAECs with adenoviral constructs of PLD1 and PLD2 wild-type potentiated hyperoxia-induced PLD activation and accumulation of O(2)(.)/reactive oxygen species (ROS). Conversely, overexpression of catalytically inactive mutants of PLD (hPLD1-K898R or mPLD2-K758R) or down-regulation of expression of PLD with PLD1 or PLD2 siRNA did not augment hyperoxia-induced [(32)P]phosphatidylbutanol accumulation and ROS generation. Hyperoxia caused rapid activation and redistribution of Rac1, and IQGAP1 to cell periphery, and down-regulation of Rac1, and IQGAP1 attenuated hyperoxia-induced tyrosine phosphorylation of Src and cortactin and ROS generation. Further, hyperoxia-mediated redistribution of Rac1, and IQGAP1 to membrane ruffles, was attenuated by PLD1 or PLD2 small interference RNA, suggesting that PLD is upstream of the Rac1/IQGAP1 signaling cascade. Finally, small interference RNA for PLD1 or PLD2 attenuated hyperoxia-induced cortactin tyrosine phosphorylation and abolished Src, cortactin, and p47(phox) redistribution to cell periphery. These results demonstrate a role of PLD in hyperoxia-mediated IQGAP1 activation through Rac1 in tyrosine phosphorylation of Src and cortactin, as well as in p47(phox) translocation and ROS formation in human lung endothelial cells.
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