Direct and specific inactivation of protein tyrosine kinases in the Src and FGFR families by reversible cysteine oxidation.

ABSTRACT: Accumulating evidence suggests that protein tyrosine phosphorylation-based signaling pathways are under the regulation of reactive oxygen species. Although protein tyrosine phosphatases are directly regulated by reversible oxidation, it is not clear whether protein tyrosine kinases (PTKs) are also directly regulated by reduction/oxidation (redox). In this study we report a mechanism of direct oxidative inactivation specific for the PTKs in the Src and fibroblast growth factor receptor (FGFR) families, key enzymes in mammalian signal transduction. Src is fully active when reduced and retains 8-25% of the full activity toward various substrates when oxidized. This inactivation is caused by oxidation of a specific cysteine residue (Cys-277), which results in homodimerization of Src linked by

SUBMITTER: Kemble DJ 

PROVIDER: S-EPMC2663993 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature