A druggable redox switch on SHP1 controls macrophage inflammation - PubMed
5 hours ago
- #SHP1
- #redox signaling
- #macrophage inflammation
- A druggable redox switch on SHP1 controls macrophage inflammation.
- Post-translational redox modification of cysteine residues is important for immune cell regulation, especially in macrophage cytokine responses.
- Deep redox proteomics identified 788 in vivo redox-regulated cysteines across immune-relevant protein domains.
- A novel cysteine activation site (C102) on SHP1 was discovered, enabling cysteine-directed pharmacology.
- A selective covalent agonist (SCA) was developed to target C102, relieving autoinhibition and activating SHP1.
- SCA engages SHP1 C102, antagonizing IRAK signaling and reducing LPS-induced proinflammatory cytokine production in macrophages.
- The study provides a compendium of redox-regulated sites for therapeutic development in immune-related diseases.