Redox Regulation of Epidermal Growth Factor Receptor Signaling Through Cysteine Oxidation
Overview
Authors
Affiliations
Epidermal growth factor receptor (EGFR) exemplifies the family of receptor tyrosine kinases that mediate numerous cellular processes, including growth, proliferation, and differentiation. Moreover, gene amplification and EGFR mutations have been identified in a number of human malignancies, making this receptor an important target for the development of anticancer drugs. In addition to ligand-dependent activation and concomitant tyrosine phosphorylation, EGFR stimulation results in the localized generation of H(2)O(2) by NADPH-dependent oxidases. In turn, H(2)O(2) functions as a secondary messenger to regulate intracellular signaling cascades, largely through the modification of specific cysteine residues within redox-sensitive protein targets, including Cys797 in the EGFR active site. In this review, we highlight recent advances in our understanding of the mechanisms that underlie redox regulation of EGFR signaling and how these discoveries may form the basis for the development of new therapeutic strategies for targeting this and other H(2)O(2)-modulated pathways.
Protein phosphatase PP2Cα S-glutathionylation regulates cell migration.
Kukulage D, Samarasinghe K, Matarage Don N, Shivamadhu M, Shishikura K, Schiff W J Biol Chem. 2024; 300(10):107784.
PMID: 39303918 PMC: 11530597. DOI: 10.1016/j.jbc.2024.107784.
Reactive Oxygen Species Mechanisms that Regulate Protein-Protein Interactions in Cancer.
Iliadis S, Papanikolaou N Int J Mol Sci. 2024; 25(17).
PMID: 39273204 PMC: 11395503. DOI: 10.3390/ijms25179255.
Reactive oxygen species activate the Drosophila TNF receptor Wengen for damage-induced regeneration.
Esteban-Collado J, Fernandez-Manas M, Fernandez-Moreno M, Maeso I, Corominas M, Serras F EMBO J. 2024; 43(17):3604-3626.
PMID: 39020149 PMC: 11377715. DOI: 10.1038/s44318-024-00155-9.
Martinez-Jaramillo E, Jamali F, Abdalbari F, Abdulkarim B, Jean-Claude B, Telleria C Cancers (Basel). 2024; 16(13).
PMID: 39001381 PMC: 11240359. DOI: 10.3390/cancers16132319.
Mendes C, Lemos I, Hipolito A, Abreu B, Freitas-Dias C, Martins F Biosci Rep. 2024; 44(7).
PMID: 38990147 PMC: 11292474. DOI: 10.1042/BSR20240752.