Abstract
The non-receptor-protein tyrosine kinase c-Src is overexpressed and activated in a large number of human
cancers, in which it is associated with tumor development and progression. Canonical regulation takes place
by means of an alternative phosphorylation of tyrosine residues Tyr419 for activation and Tyr530 for
inactivation. An independent redox regulation mechanism, involving cysteine residues, has also been
proposed, in which oxidation activates the enzyme. Here we present a kinetic analysis of the effect of
N-acetyl-l-cysteine (NAC) on c-Src, demonstrating that reduction reverts the oxidation-driven activation. In
cancer cells, we show that NAC treatment produces an increase in specifically labeled reduced thiols of c-Src
cysteines, thus confirming a redox transition. In addition to a decrease in Tyr419 phosphorylation, this leads
to a massive shift of c-Src from plasma membranes where its active form is located to endolysosomal
compartments. With the objective of deciphering the complex issue of c-Src regulation and of devising new
strategies to revert its activation in cancers, redox regulation thus emerges as a promising area for study.
Lingua originale | English |
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pagine (da-a) | 1566-1572 |
Numero di pagine | 7 |
Rivista | FREE RADICAL BIOLOGY & MEDICINE |
Stato di pubblicazione | Pubblicato - 2008 |
Keywords
- N-acetyl-l-cysteine
- c-Src