Roles of superoxide radical anion in signal transduction mediated by reversible regulation of protein-tyrosine phosphatase 1B

William C. Barrett, Jon P. DeGnore, Yen Fang Keng, Zhong-Yin Zhang, Moon B. Yim, P. Boon Chock

Research output: Contribution to journalArticle

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Abstract

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 O2- is kinetically more efficient and chemically more specific oxidant than H2O2 for inactivating PTP-1B. The second-order rate constant for the O2-- and H2O2-mediated inactivation is 334 ± 45 M-1 s-1 and 42.8 ± 3.8 M-1 s-1, respectively. PTP-1B oxidized by H2O2 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 O2- 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.

Original languageEnglish (US)
Pages (from-to)34543-34546
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number49
DOIs
StatePublished - Dec 3 1999
Externally publishedYes

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
Signal transduction
Superoxides
Anions
Signal Transduction
Protein Tyrosine Phosphatases
Derivatives
Glutaredoxins
Dithiothreitol
Epidermal Growth Factor
Oxidants
Methionine
Protein-Tyrosine Kinases
Glutathione
Tyrosine
Rate constants
Reactive Oxygen Species
Catalytic Domain
Intercellular Signaling Peptides and Proteins
Demonstrations

ASJC Scopus subject areas

  • Biochemistry

Cite this

Roles of superoxide radical anion in signal transduction mediated by reversible regulation of protein-tyrosine phosphatase 1B. / Barrett, William C.; DeGnore, Jon P.; Keng, Yen Fang; Zhang, Zhong-Yin; Yim, Moon B.; Chock, P. Boon.

In: Journal of Biological Chemistry, Vol. 274, No. 49, 03.12.1999, p. 34543-34546.

Research output: Contribution to journalArticle

Barrett, William C. ; DeGnore, Jon P. ; Keng, Yen Fang ; Zhang, Zhong-Yin ; Yim, Moon B. ; Chock, P. Boon. / Roles of superoxide radical anion in signal transduction mediated by reversible regulation of protein-tyrosine phosphatase 1B. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 49. pp. 34543-34546.
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