Pervanadate reveals a new redox model of cellular phosphotyrosine 1 signaling C4PR_LIV

Protein tyrosine phosphorylation (pTyr) is controlled by protein tyrosine kinases and phosphatases (PTPs) and allows cells to sense and respond to changes in their environment. Pervanadate is a widely used chemical tool that induces global pTyr, a phenomenon attributed to its properties as a PTP inhibitor, leading to the pervasive view that PTPs are the primary regulators of pTyr in cell culture. Here, we questioned this assumption and reveal that pervanadate not only inhibits PTPs, but also directly activates the SRC tyrosine kinase by oxidizing specific cysteine residues. Ourstudy provides mechanistic insight into how cysteine oxidation relieves the autoinhibited state of SRC and alters phosphopeptide binding. We further demonstrate that these cysteine residues are required for SRC to drive cellular overgrowth.