Year: 2026
Type: article
Abstract: Dynamic regulation of protein tyrosine phosphorylation (pTyr) by kinases and phosphatases enables cells to sense and respond to environmental changes. The widely used chemical pervanadate induces the accumulation of pTyr in mammalian cell lines. This effect is primarily attributed to its inhibition of protein tyrosine phosphatases (PTPs), leading to the assertion that PTPs are master gatekeepers of intracellular pTyr homeostasis. Here, we used several approaches to reveal that pervanadate disrupted cellular redox homeostasis and directly activated tyrosine kinases of the SRC family through the oxidation of specific cysteine residues. Mass spectrometry and biophysical approaches showed that pervanadate-induced oxidation of cysteine-188 and cysteine-280 activated SRC by disrupting autoinhibitory intramolecular interactions between the catalytic domain and the SH2/SH3 domains and by impairing SH2 domain binding to phosphopeptides, including the regulatory carboxyl-terminal tail phosphotyrosine-530. Redox-sensitive cysteine residues were essential for SRC to promote the overgrowth of mouse fibroblasts. Our findings call for a reevaluation of pervanadate-based experiments and demonstrate that SRC cysteines control its oncogenic properties.
Source: Science Signaling
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Signalling mechanisms that determine the rate of ageing, G2876198418, MechanoROS-T: Exploring mechanoregulated hydrogen peroxide as a mechanism of T cell activation, Redox signalling through Ser/Thr protein kinase networks, G4537093758, Receptor tyrosine phosphatases in physiology and disease., G514749587, Understanding complexity of post-translation modifications by enhancing UK capability for top-down proteomics, Analysis of the dynamic sulfotyrosine proteome., G7598680444, G7966986318, G9000324276
OpenAlex ID: W7125009344