| First Author | Tsutsumi R | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 466 |
| PubMed ID | 28878211 | Mgi Jnum | J:251949 |
| Mgi Id | MGI:5926792 | Doi | 10.1038/s41467-017-00503-w |
| Citation | Tsutsumi R, et al. (2017) Assay to visualize specific protein oxidation reveals spatio-temporal regulation of SHP2. Nat Commun 8(1):466 |
| abstractText | Reactive oxygen species are produced transiently in response to cell stimuli, and function as second messengers that oxidize target proteins. Protein-tyrosine phosphatases are important reactive oxygen species targets, whose oxidation results in rapid, reversible, catalytic inactivation. Despite increasing evidence for the importance of protein-tyrosine phosphatase oxidation in signal transduction, the cell biological details of reactive oxygen species-catalyzed protein-tyrosine phosphatase inactivation have remained largely unclear, due to our inability to visualize protein-tyrosine phosphatase oxidation in cells. By combining proximity ligation assay with chemical labeling of cysteine residues in the sulfenic acid state, we visualize oxidized Src homology 2 domain-containing protein-tyrosine phosphatase 2 (SHP2). We find that platelet-derived growth factor evokes transient oxidation on or close to RAB5+/ early endosome antigen 1- endosomes. SHP2 oxidation requires NADPH oxidases (NOXs), and oxidized SHP2 co-localizes with platelet-derived growth factor receptor and NOX1/4. Our data demonstrate spatially and temporally limited protein oxidation within cells, and suggest that platelet-derived growth factor-dependent "redoxosomes," contribute to proper signal transduction.Protein-tyrosine phosphatases (PTPs) are thought to be major targets of receptor-activated reactive oxygen species (ROS). Here the authors describe a method that allows the localized visualization of oxidized intermediates of PTPs inside cells during signaling, and provide support for the "redoxosome" model. |
