Reactivation of oxidized PTP1B and PTEN by Thioredoxin 1

Schwertassek, U., Haque, A., Krishnan, N., Greiner, R., Weingarten, L., Dick, T. P., Tonks, N. K. (2014) Reactivation of oxidized PTP1B and PTEN by Thioredoxin 1. Febs Journal, 281 (16). pp. 3545-3558. ISSN 1742-464X

URL: http://www.ncbi.nlm.nih.gov/pubmed/24976139
DOI: 10.1111/febs.12898

Abstract

The transient inactivation of protein phosphatases contributes to the efficiency and temporal control of kinase-dependent signal transduction. In particular, members of the protein tyrosine phosphatase family are known to undergo reversible oxidation of their active site cysteine. The thiol oxidation step requires activation of co-localized NADPH oxidases and is mediated by locally produced ROS, in particular H2 O2 . How oxidized phosphatases are returned to the reduced active state is less well studied. Both major thiol reductive systems, the thioredoxin and the glutathione systems, have been implicated in the reactivation of phosphatases. Here, we show that the protein tyrosine phosphatase PTP1B and the dual-specificity phosphatase PTEN are preferentially reactivated by the thioredoxin system. We show that inducible depletion of TRX1 slows down PTEN re-activation in intact living cells. Finally, using a mechanism-based trapping approach we demonstrate direct thiol disulfide exchange between the active sites of thioredoxin and either phosphatase. The application of thioredoxin trapping mutants represents a complementary approach to direct assays of PTP oxidation in elucidating the significance of redox regulation of PTP function in the control of cell signaling. This article is protected by copyright. All rights reserved.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN
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
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date Deposited: 11 Jul 2014 19:17
Last Modified: 16 Oct 2015 15:05
PMCID: PMC4162488
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30482

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving