Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo
Open accessAbstract
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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Phosphatases are inhibited by ROS.
“In general, phosphatases are inhibited by ROS11, whereas kinases may be inhibited or activated12.”
From ROS in cancer therapy: the bright side of the moon (2020) · cites this paper as [11]
Protein tyrosine phosphatase 1B was the first phosphatase demonstrated to be inhibited by ROS under physiological conditions.
“Protein tyrosine phosphatase 1B was the first phosphatase demonstrated to be inhibited by ROS under physiological conditions 49, 50.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [50]
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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
- bronze
- doi.org
- Licence
- 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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