title: Redox regulation of epidermal growth factor receptor signaling through cysteine oxidation.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Thu H
authors.initials: TH
authors.lastname: Truong
authors.forename: Kate S
authors.initials: KS
authors.lastname: Carroll
mesh_terms: D003545:Cysteine / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013434:Sulfenic Acids / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D013434:Sulfenic Acids; D004815:Epidermal Growth Factor; D006861:Hydrogen Peroxide; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D066246:ErbB Receptors; D003545:Cysteine