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Reactivation of oxidized PTP1B and PTEN by thioredoxin 1
Author(s) -
Schwertassek Ulla,
Haque Aftabul,
Krishnan Navasona,
Greiner Romy,
Weingarten Lars,
Dick Tobias P.,
Tonks Nicholas K.
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12898
Subject(s) - pten , phosphatase , protein tyrosine phosphatase , thioredoxin , thioredoxin reductase , immunoprecipitation , biochemistry , chemistry , microbiology and biotechnology , signal transduction , cysteine , glutathione , phosphorylation , biology , enzyme , pi3k/akt/mtor pathway , gene
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 colocalized NADPH oxidases and is mediated by locally produced reactive oxygen species, in particular H 2 O 2 . 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 thioredoxin 1(TRX1) slows PTEN reactivation in intact living cells. Finally, using a mechanism‐based trapping approach, we demonstrate direct thiol disulphide 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. Structured digital abstractTRX1 physically interacts with PTP1B by anti tag coimmunoprecipitation ( 1 , 2 )