Document Detail


Redox regulation of epidermal growth factor receptor signaling through cysteine oxidation.
MedLine Citation:
PMID:  23186290     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Thu H Truong; Kate S Carroll
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2012-12-05
Journal Detail:
Title:  Biochemistry     Volume:  51     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-18     Completed Date:  2013-02-19     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9954-65     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cysteine / metabolism*
Epidermal Growth Factor / metabolism
Humans
Hydrogen Peroxide / metabolism*
Membrane Glycoproteins / metabolism
NADPH Oxidase / metabolism
Oxidation-Reduction
Phosphorylation
Receptor, Epidermal Growth Factor / genetics,  physiology*
Second Messenger Systems / physiology
Signal Transduction / physiology*
Sulfenic Acids / metabolism
Grant Support
ID/Acronym/Agency:
GM102187/GM/NIGMS NIH HHS; R01 GM102187/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/CYBB protein, human; 0/Membrane Glycoproteins; 0/Sulfenic Acids; 62229-50-9/Epidermal Growth Factor; BBX060AN9V/Hydrogen Peroxide; EC 1.6.3.1/NADPH Oxidase; EC 2.7.10.1/Receptor, Epidermal Growth Factor; K848JZ4886/Cysteine
Comments/Corrections

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