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.
von Montfort
Claudia
C
Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, D-40225 Düsseldorf, Germany.
Sharov
Victor S
VS
Metzger
Sabine
S
Schöneich
Christian
C
Sies
Helmut
H
Klotz
Lars-Oliver
LO
D000595:Amino Acid Sequence; D001665:Binding Sites; D003545:Cysteine / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D026082:Singlet Oxygen / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
D026082:Singlet Oxygen; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D003545:Cysteine