Regulation of receptor protein‐tyrosine phosphatase α by oxidative stress
TLDR
It is proposed that an intramolecular interaction between the spacer region (Sp) and the C‐terminus in RPTPα prohibited intermolecular interactions, and stress factors such as H2O2, UV and heat shock induced reversible, free radical‐dependent, intermolescular interactions between RPTP α and RPTPβ, suggesting an inducible switch in conformation and binding.Abstract:
The presence of two protein-tyrosine phosphatase (PTP) domains is a striking feature in most transmembrane receptor PTPs (RPTPs). The function of the generally inactive membrane-distal PTP domain (RPTP-D2) is unknown. Here we report that an intramolecular interaction between the spacer region (Sp) and the C-terminus in RPTPα prohibited intermolecular interactions. Interestingly, stress factors such as H2O2, UV and heat shock induced reversible, free radical-dependent, intermolecular interactions between RPTPα and RPTPα-SpD2, suggesting an inducible switch in conformation and binding. The catalytic site cysteine of RPTPα-SpD2, Cys723, was required for the H2O2 effect on RPTPα. H2O2 induced a rapid, reversible, Cys723-dependent conformational change in vivo, as detected by fluorescence resonance energy transfer, with cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) flanking RPTPα-SpD2 in a single chimeric protein. Importantly, H2O2 treatment stabilized RPTPα dimers, resulting in inactivation. We propose a model in which oxidative stress induces a conformational change in RPTPα-D2, leading to stabilization of RPTPα dimers, and thus to inhibition of RPTPα activity.read more
Citations
More filters
Journal ArticleDOI
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
TL;DR: This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival, ROS homeostasis and antioxidant gene regulation, mitochondrial oxidative stress, apoptosis, and aging.
Journal ArticleDOI
Protein tyrosine phosphatases: from genes, to function, to disease
TL;DR: Recent breakthroughs in understanding of the role of the PTPs in the regulation of signal transduction and the aetiology of human disease are described.
Journal ArticleDOI
Oxidant signals and oxidative stress.
TL;DR: These new studies have significantly altered the authors' understanding of how reactive oxygen species participate in diverse processes from tumourigenesis to ageing.
Journal ArticleDOI
Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate
Annette Salmeen,Jannik N. Andersen,Michael P. Myers,Tzu-Ching Meng,John A. Hinks,Nicholas K. Tonks,David Barford +6 more
TL;DR: It is proposed that this unusual protein modification both protects the active-site cysteine residue of PTP1B from irreversible oxidation to sulphonic acid and permits redox regulation of the enzyme by promoting its reversible reduction by thiols.
Journal ArticleDOI
Reactive oxygen species as mediators of angiogenesis signaling: role of NAD(P)H oxidase.
TL;DR: Recent progress is focused on the recent progress that has been made in the emerging area of NAD(P)H oxidase-derived ROS-dependent signaling in ECs, and the possible roles in angiogenesis are discussed.
References
More filters
Journal ArticleDOI
Fluorescent indicators for Ca2+based on green fluorescent proteins and calmodulin
Atsushi Miyawaki,Juan Llopis,Roger Heim,J. Michael McCaffery,Joseph A. Adams,Mitsuhiko Ikura,Mitsuhiko Ikura,Roger Y. Tsien +7 more
TL;DR: New fluorescent indicators for Ca2+ that are genetically encoded without cofactors and are targetable to specific intracellular locations are constructed and dubbed ‘cameleons’.
Journal ArticleDOI
Protein kinases and phosphatases: The Yin and Yang of protein phosphorylation and signaling
TL;DR: Although the use of PP inhibitors shows that there is significant basal PP activity in cells, it has become apparent that the activities of PPs are regulated in a sophisticated manner by a combination of targeting and regulatory subunits and by specific inhibitors.
Journal ArticleDOI
Understanding, improving and using green fluorescent proteins.
Andrew B. Cubitt,Roger Heim,Stephen Adams,Aileen E. Boyd,Larry A. Gross,Roger Y. Tsien,Roger Y. Tsien +6 more
TL;DR: The GFP originally cloned from the jellyfish Aequorea victoria has several nonoptimal properties including low brightness, a significant delay between protein synthesis and fluorescence development, and complex photoisomerization, but can be re-engineered by mutagenesis to ameliorate these deficiencies and shift the excitation and emission wavelengths, creating different colors and new applications.
Journal ArticleDOI
Epidermal Growth Factor (EGF)-induced Generation of Hydrogen Peroxide ROLE IN EGF RECEPTOR-MEDIATED TYROSINE PHOSPHORYLATION
TL;DR: In this paper, the role of reactive oxygen species (ROS) in epidermal growth factor (EGF) signaling was investigated, and the dependence of H2O2 production on the intrinsic tyrosine kinase activity of the EGF receptor and the autophosphorylation sites located in its COOH-terminal tail was investigated.
Journal ArticleDOI
Reversible Inactivation of Protein-tyrosine Phosphatase 1B in A431 Cells Stimulated with Epidermal Growth Factor
TL;DR: The results indicate that the activation of a receptor tyrosine kinase by binding of the corresponding growth factor may not be sufficient to increase the steady state level of protein tyrosines phosphorylation in cells and that concurrent inhibition of protein-tyrosine phosphatases by H2O2 might also be required.