Redox regulation of the protein tyrosine phosphatase PTP1B in cancer cells

Lou, Y.-W., Chen, Y.-Y., Hsu, S.-F., Chen, R.-K., Lee, C.-L., Khoo, K.-H., Tonks, N. K., Meng, T.-C. (January 2008) Redox regulation of the protein tyrosine phosphatase PTP1B in cancer cells. FEBS Journal, 275 (1). pp. 69-88.

URL: http://www.ncbi.nlm.nih.gov/pubmed/18067579
DOI: 10.1111/j.1742-4658.2007.06173

Abstract

The oxidation and inactivation of protein tyrosine phosphatases is one mechanism by which reactive oxygen species influence tyrosine phosphorylation-dependent signaling events and exert their biological functions. In the present study, we determined the redox status of endogenous protein tyrosine phosphatases in HepG2 and A431 human cancer cells, in which reactive oxygen species are produced constitutively. We used mass spectrometry to assess the state of oxidation of the catalytic cysteine residue of endogenous PTP1B and show that this residue underwent both reversible and irreversible oxidation to high stoichiometry in response to intrinsic reactive oxygen species production. In addition, our data show that the oxidation of PTP1B is specific to the active site Cys, with the other Cys residues in the protein remaining in a reduced state. Treatment of these cells with diphenyleniodonium, an inhibitor of NADPH oxidases, decreased reactive oxygen species levels. This resulted in inhibition of protein tyrosine phosphatase oxidation, concomitant with decreased tyrosine phosphorylation of cellular proteins and inhibition of anchorage-independent cell growth. Therefore, our data also suggest that the high level of intrinsic reactive oxygen species may contribute to the transformed phenotype of HepG2 and A431 cells via constitutive inactivation of cellular protein tyrosine phosphatases.

Item Type: Paper
Uncontrolled Keywords: DPI, diphenyleniodonium Nox, NADPH oxidase PTP, protein tyrosine phosphatase ROS, reactive oxygen species RPTP, receptor-like protein tyrosine phosphatase
Subjects: diseases & disorders > cancer
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase
CSHL Authors:
Communities: CSHL labs > Tonks lab
Depositing User: Matt Covey
Date: January 2008
Date Deposited: 25 Feb 2013 20:47
Last Modified: 25 Feb 2013 20:47
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27604

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