Cited by 1,040Protein Tyrosine PhosphatasesRedox biology and oxidative stressProtein Kinase Regulation and GTPase Signaling

Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo

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Meng, Tzu-Ching, Fukada, Toshiyuki, Tonks, Nicholas K·2002·Molecular Cell

Abstract

We have investigated the regulation of protein tyrosine phosphatases (PTPs) by reactive oxygen species (ROS) in a cellular environment. We demonstrate that multiple PTPs were reversibly oxidized and inactivated following treatment of Rat-1 cells with H(2)O(2) and that inhibition of PTP function was important for ROS-induced mitogenesis. Furthermore, we show transient oxidation of the SH2 domain containing PTP, SHP-2, in response to PDGF that requires association with the PDGFR. Our results indicate that SHP-2 inhibits PDGFR signaling and suggest a mechanism by which autophosphorylation of the PDGFR occurs despite its association with SHP-2. The data suggest that several PTPs may be regulated by oxidation and that characterization of this process may define novel links between specific PTPs and particular signaling pathways in vivo.

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Crossref · 10.1016/s1097-2765(02)00445-8

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Authors
Meng, T.-C., Fukada, T., & Tonks, N. K.
Affiliations
Cold Spring Harbor Laboratory (US)
Corresponding author
Tonks, Nicholas K
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2002-02
Volume
9
Issue
2
Pages
387-399
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2043549608
Cited by
1,040
References
50
Citations by year
2026: 16 · 2025: 19 · 2024: 19 · 2023: 19 · 2022: 25 · 2021: 36 · 2020: 26 · 2019: 34 · 2018: 32 · 2017: 32 · 2016: 36 · 2015: 35 · 2014: 60 · 2013: 56 · 2012: 44
FWCI
24.57
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • Naito Foundation
  • Japan Society for the Promotion of Science
  • National Institutes of Health (R01-GM55989)
  • Cold Spring Harbor Laboratory (P30-CA45508)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
protein tyrosine phosphatase, reversible oxidation, reactive oxygen species, hydrogen peroxide, SHP2, PDGF receptor, PDGFR signaling, mitogenesis, SH2 domain, autophosphorylation, enzyme inactivation, signaling regulation
MeSH terms
Animals, Cells, Cultured, Fibroblasts, Hydrogen Peroxide, Mitosis, Oxidation-Reduction, Phosphorylation, Platelet-Derived Growth Factor, Protein Processing, Post-Translational, Signal Transduction, Protein Tyrosine Phosphatases, Reactive Oxygen Species, Receptors, Platelet-Derived Growth Factor, Intracellular Signaling Peptides and Proteins, Rats, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatase, Non-Receptor Type 11, SH2 Domain-Containing Protein Tyrosine Phosphatases

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