ArticleProceedings of the National Academy of Sciences of the United States of America2023
ROCK2 interacts with p22phox to phosphorylate p47phox and to control NADPH oxidase activation in human monocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 17 citations in OpenAlex.
- Inhibition of ROCK2 via KD025/Belumosudil Alleviates Hypertensive End-Organ Damage.Hypertension (Dallas, Tex. : 1979) · 2026Article
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Targeting CYBA inhibits hepatic metastasis of pancreatic cancer through AKT/MLC2 pathway.Acta pharmacologica Sinica · 2026Article
- ROCK signaling at the crossroads of redox stress, mitochondrial dynamics, and metabolic disease.Redox biology · 2026Review
- Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology.Antioxidants (Basel, Switzerland) · 2026Review
- Lithospermic Acid Improves Doxorubicin-Induced Cardiomyopathy Through Sirtuin-3-Mediated Deacetylation of p53.Phytotherapy research : PTR · 2026Article
- miR-19b-3p engineered adipose-derived stem cell exosomes attenuate acute liver failure via promoting tissue repair and microenvironment remodeling.Materials today. Bio · 2026Article
- Inhaled bovine lactoferrin modulates the p47phox-MPO-NETosis axis in acute lung injury: implications for bioengineered nanomedicine in respiratory infections.Frontiers in immunology · 2026Article
- ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions.Molecular biomedicine · 2025Review
- A host-pathogen metabolic synchrony that facilitates disease tolerance.Nature communications · 2025Article
- Neuroinflammation-A Crucial Factor in the Pathophysiology of Depression-A Comprehensive Review.Biomolecules · 2025Review
- Article
- NCF-1 plays a pivotal role in the survival of adenocarcinoma cells of pancreatic and gastric origins.In vitro cellular & developmental biology. Animal · 2024Article
- Insights into Alkaline Phosphatase Anti-Inflammatory Mechanisms.Biomedicines · 2024Review
- Free Radical Inhibition Using a Water-Soluble Curcumin Complex, NDS27: Mechanism Study Using EPR, Chemiluminescence, and Docking.Antioxidants (Basel, Switzerland) · 2024Article
- Tumour-associated macrophages: versatile players in the tumour microenvironment.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
8 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monocytes play a key role in innate immunity by eliminating pathogens, releasing high levels of cytokines, and differentiating into several cell types, including macrophages and dendritic cells. Similar to other phagocytes, monocytes produce superoxide anions through the NADPH oxidase complex, which is composed of two membrane proteins (p22phox and gp91phox/NOX2) and four cytosolic proteins (p47phox, p67phox, p40phox and Rac1). The pathways involved in NADPH oxidase activation in monocytes are less known than those in neutrophils. Here, we show that p22phox is associated with Rho-associated coiled-coil kinase 2 (ROCK2) in human monocytes but not neutrophils. This interaction occurs between the cytosolic region of p22phox (amino acids 132 to 195) and the coiled-coil region of ROCK2 (amino acids 400 to 967). Interestingly, ROCK2 does not phosphorylate p22phox, p40phox, p67phox, or gp91phox in vitro but phosphorylates p47phox on Ser304, Ser315, Ser320 and Ser328. Furthermore, KD025, a selective inhibitor of ROCK2, inhibited reactive oxygen species (ROS) production and p47phox phosphorylation in monocytes. Specific inhibition of ROCK2 expression in THP1-monocytic cell line by siRNA inhibited ROS production. These data show that ROCK2 interacts with p22phox and phosphorylates p47phox, and suggest that p22phox could be a shuttle for ROCK2 to allow p47phox phosphorylation and NADPH oxidase activation in human monocytes.
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