Global Proteomic Assessment of the Classical Protein-Tyrosine Phosphatome and “Redoxome”

SummaryProtein-tyrosine phosphatases (PTPs), along with protein-tyrosine kinases, play key roles in cellular signaling. All Class I PTPs contain an essential active site cysteinyl residue, which executes a nucleophilic attack on substrate phosphotyrosyl residues. The high reactivity of the catalytic cysteine also predisposes PTPs to oxidation by reactive oxygen species, such as H2O2. Reversible PTP oxidation is emerging as an important cellular regulatory mechanism and might contribute to diseases such as cancer. We exploited these unique features of PTP enzymology to develop proteomic methods, broadly applicable to cell and tissue samples, that enable the comprehensive identification and quantification of expressed classical PTPs (PTPome) and the oxidized subset of the PTPome (oxPTPome). We find that mouse and human cells and tissues, including cancer cells, display distinctive PTPomes and oxPTPomes, revealing additional levels of complexity in the regulation of protein-tyrosine phosphorylation in normal and malignant cells.

Graphical AbstractFigure optionsDownload high-quality image (318 K)Download as PowerPoint slideHighlights
► Proteomic approach monitors classical protein-tyrosine phosphatase (PTP) expression
► Modified method measures the fraction of PTPs that are oxidized
► Different cancer cell lines contain unique PTP oxidation profiles
► Method can be combined with phosphotyrosine proteomics to suggest PTP substrates