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Redox Regulated Growth Factor Survival Signalling.
MedLine Citation:
PMID:  23198948     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Significance: Once thought of as unwanted by-products of cellular respiration in eukaryotes, reactive oxygen species (ROS) have been shown to facilitate essential physiological roles. It is now understood that ROS are critical mediators of intracellular signalling. Control of signal transduction downstream of growth factor receptors by ROS is a complex process whose details are only recently coming to light. Recent Advances: Indeed, recent evidence points to control of signal propagation by ROS at multiple levels in the typical cascade. Growth factor stimulation activates NADPH oxidases (Noxs) at the membrane, producing superoxide in the extracellular matrix, which is catalyzed to the membrane-permeable hydrogen peroxide that mediates intracellular signalling events. Critical Issues: The potential for hydrogen peroxide, however, to disrupt cellular functions by damaging proteins and nucleic acids demands that its levels are kept in check by receptor associated peroxiredoxins. This interplay of Nox and peroxiredoxin activity moderates levels of hydrogen peroxide sufficiently to modify signalling partners locally. Among the best studied of these partners are redox-controlled phosphatases that are inactivated by hydrogen peroxide. Phosphatases regulate signal propagation downstream of receptors and thus their inactivation allows a further level of control. Transmission of information further downstream to targets such as transcription factors, themselves regulated by ROS, completes this pathway. Future Directions: Thus, signal propagation or attenuation can be dictated by ROS at multiple points. Given the complex nature of these processes we envisage the emerging trends in the field of redox signalling in the context of growth factor stimulation.
Authors:
John F Woolley; Aoife Corcoran; Gillian Groeger; William D Landry; Thomas G Cotter
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-2
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University College Cork, Dept. of Biochemistry, Cork City, Cork, City, Ireland, n/a; j.woolley@ucc.ie.
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