uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Oxidation sensitivity of the catalytic cysteine of the protein-tyrosine phosphatases SHP-1 and SHP-2
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Show others and affiliations
2007 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 43, no 1, 100-110 p.Article in journal (Refereed) Published
Abstract [en]

Reversible oxidation of the catalytic cysteine of protein-tyrosine phosphatases (PTPs) has emerged as a putative mechanism of activity regulation by physiological cell stimulation with growth factors, and by cell treatments with adverse agents such as UV irradiation. We compared SHP-1 and SHP-2, two structurally related cytoplasmic protein-tyrosine phosphatases with different cellular functions and cell-specific expression patterns, for their intrinsic susceptibility to oxidation by H(2)O(2). The extent of oxidation was monitored by detecting the modification of the PTP catalytic cysteine by three different methods, including a modified in-gel PTP assay, alkylation with a biotinylated iodoacetic acid derivative, and an antibody against oxidized PTPs. Dose-response curves for oxidation of the catalytic domains of SHP-1 and SHP-2 were similar. SHP-1 and -2 require relatively high H(2)O(2) concentrations for oxidation (half-maximal oxidation at 0.1-0.5 mM). For SHP-1, the SH2 domains had a significant protective function with respect to oxidation. In EOL-1 cells, SHP oxidation by exogenous H(2)O(2) in general and SHP-2 oxidation in particular was strongly diminished compared to HEK293 cells, at least partially related to a generally lower oxidant sensitivity of the EOL-1 cells. The data suggest that the differential cell functions of SHP-1 and SHP-2 are not related to differences in oxidation sensitivity. The modulating effects of SH2 domains for oxidation of these PTPs are in support of an enhanced oxidation susceptibility of activated SHPs.

Place, publisher, year, edition, pages
2007. Vol. 43, no 1, 100-110 p.
Keyword [en]
Protein-tyrosine phosphatase, Oxidation, Modified in-gel assay, Ox-PTP antibody, SH2 domains
National Category
Medical and Health Sciences Biological Sciences
URN: urn:nbn:se:uu:diva-120047DOI: 10.1016/j.freeradbiomed.2007.03.021ISI: 000247395000012PubMedID: 17561098OAI: oai:DiVA.org:uu-120047DiVA: diva2:302338
Available from: 2010-03-05 Created: 2010-03-05 Last updated: 2011-02-05Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Genetics and Pathology
In the same journal
Free Radical Biology & Medicine
Medical and Health SciencesBiological Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 187 hits
ReferencesLink to record
Permanent link

Direct link