Singlet oxygen inactivates protein tyrosine phosphatase-1B by oxidation of the active site cysteine.

Singlet oxygen ((1)O(2)), an electronically excited form of molecular oxygen, is a mediator of biological effects of ultraviolet A radiation, stimulating signaling cascades in human cells. We demonstrate here that (1)O(2) generated by photosensitization or by thermodecomposition of 3,3'-(1,4-naphthylidene)dipropionate-1,4-endoperoxide inactivates isolated protein tyrosine phosphatases (PTPases). PTPase activities of PTP1B or CD45 were abolished by low concentrations of (1)O(2), but were largely restored by post-treatment with dithiothreitol. Electrospray ionization mass spectrometry analysis of tryptic digests of PTP1B exposed to (1)O(2) revealed oxidation of active-site Cys215 as the only cysteine residue oxidized. In summary, (1)O(2) may activate signaling cascades by interfering with phosphotyrosine dephosphorylation.