Roles of Superoxide Radical Anion in Signal Transduction Mediated by Reversible Regulation of Protein-tyrosine Phosphatase 1B
Growth factors induce intracellular production of reactive oxygen species in non-phagocytic cells and elevation of their phosphorylated protein tyrosine level. The latter can be achieved by activating protein-tyrosine kinases and/or inactivating protein-tyrosine phosphatases (PTPs). A highly abundan...
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Published in | The Journal of biological chemistry Vol. 274; no. 49; pp. 34543 - 34546 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
03.12.1999
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Subjects | |
Online Access | Get full text |
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Summary: | Growth factors induce intracellular production of reactive oxygen species in non-phagocytic cells and elevation of their phosphorylated
protein tyrosine level. The latter can be achieved by activating protein-tyrosine kinases and/or inactivating protein-tyrosine
phosphatases (PTPs). A highly abundant PTP, PTP-1B, is known to be inactivated by oxidation of its catalytic site Cys-215.
We show that OÂ·Ì 2 is kinetically more efficient and chemically more specific oxidant than H 2 O 2 for inactivating PTP-1B. The second-order rate constant for the OÂ·Ì 2 - and H 2 O 2 -mediated inactivation is 334 ± 45 m
â1 s â1 and 42.8 ± 3.8 m
â1 s â1 , respectively. PTP-1B oxidized by H 2 O 2 exhibits significantly more oxidized methionine residues and shows a lower degree of reversibility. The initial oxidative
product, the Cys-215 sulfenic derivative, can easily be oxidized further to its irreversible sulfinic and sulfonic derivatives.
This step is prevented by glutathionylation of the sulfenic derivative to form a S -glutathionylated PTP-1B, which can be reactivated by dithiothreitol or thioltransferase. Thus, a signal transduction mechanism
mediated by the OÂ·Ì 2 and the participation of glutathione is proposed for the regulation of PTP-1B. This mechanism is supported by the in vivo demonstration that glutathionylated PTP-1B at Cys-215 is formed in A431 cells when they were treated with epidermal growth
factor. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.49.34543 |