Regulation of PTP1B via glutathionylation of the active site cysteine 215

A mechanism for the in vivo regulation of protein tyrosine phosphatase 1B (PTP1B) is the glutathionylation of the active site cysteine 215. Mass spectrometry reveals that treatment of PTP1B with diamide and reduced glutathione or with only glutathione disulfide causes modification in which the cysteine residues are oxidixed to mixed disulfides with glutathione. Results also indicate that the inactivated form of the phosphatase is a glutathionyl mixed disulfide.