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Updated: May 15, 2026
08:37
Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
Published on: November 5, 2014
Activation of PAD4 in NET formation
Amanda S Rohrbach1, Daniel J Slade, Paul R Thompson
1Department of Chemical Physiology, The Scripps Research Institute La Jolla, CA, USA.
Frontiers in Immunology
|December 25, 2012
Summary
Peptidylarginine deiminases (PADs) convert arginine to citrulline. PAD4 enzyme activation and neutrophil extracellular trap (NET) formation involve signaling pathways and reactive oxygen species, crucial for innate immunity.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- Peptidylarginine deiminases (PADs) catalyze the conversion of arginine to citrulline.
- PAD4, expressed in granulocytes, is critical for neutrophil extracellular trap (NET) formation through histone citrullination.
- Histone citrullination is believed to facilitate NET formation by decondensing chromatin and enabling DNA expulsion.
Purpose of the Study:
- To elucidate the stimuli and signaling pathways governing PAD4 activation and NET formation.
- To explore the role of reactive oxygen species in PAD4-mediated NET formation.
- To provide a foundation for understanding PAD4 function and developing targeted inhibitors.
Main Methods:
- Review of existing literature on PAD4 structure, function, and activation.
- Analysis of signaling pathways implicated in PAD4 activation.
- Discussion of stimuli leading to NET formation.
Main Results:
- Multiple stimuli trigger PAD4 activation and NET formation.
- Reactive oxygen species play a role in this signaling process.
- Understanding PAD4 activation pathways is key to innate immunity research.
Conclusions:
- The precise mechanisms of PAD4 activation remain largely unknown.
- Identifying signaling intermediates could lead to novel therapeutics for NET-related diseases.
- Further research into PAD4 regulation is vital for innate immunity and drug development.
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