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Redox Regulation of PTPs in Metabolism: Focus on Assays

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Protein Tyrosine Phosphatase Control of Metabolism

Abstract

Protein-tyrosine phosphatases (PTPs), along with protein-tyrosine kinases (PTKs), are the key regulators of phosphotyrosine signaling, and therefore are important contributors to normal metabolism and metabolic disease. Over the past 10 years, reactive oxygen species (ROS), which had long been viewed as toxic by-products of metabolism, have been recast as important second messengers, which act, at least in part, to regulate PTP activity by reversible oxidation. For example, ROS-catalyzed PTP oxidation can transiently inhibit PTP enzymatic activity and facilitate ligand-induced receptor tyrosine kinase (RTK) signaling. Identifying ROS-inactivated PTPs represents a key challenge to understanding the role of PTPs and redox regulation in physiology and pathology. Here, we briefly review ROS regulation of PTPs, focusing on existing assays and new approaches to identify and quantify PTP oxidation.

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Abbreviations

ABP:

Activity-based probe

AGE:

Advanced glycation end product

Alk-β-KE:

Alkyne β-ketoester

BBP-Biotin:

α-Bromobenzylphosphonate biotin

BP1:

Biotin-1,3-cyclopentanedione

DSP:

Dual-specificity PTP

DTT:

Dithiothreitol

EGF:

Epidermal growth factor

ER:

Endoplasmic reticulum

FFA:

Free fatty acid

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

GPX:

Glutathione peroxidase

GRX:

Glutaredoxin

GSH:

Glutathione

H2O2 :

Hydrogen peroxide

HFD:

High-fat diet

IAA:

Iodoacetic acid

IAM:

Iodoacetamide

IAP-Biotin:

Iodoacetylpolyethylene oxide biotin

IB:

Immunoblot

IF:

Immunofluorescence

IKK:

Inhibitor of κB kinase

IL:

Interleukin

IP:

Immunoprecipitation

IR:

Insulin receptor

IRS:

Insulin receptor substrate

JNK:

c-Jun NH2-terminal kinase

LA:

α-Lipoic acid

LC-MS/MS:

Liquid chromatography-tandem mass spectrometry

MAPK:

Mitogen-activated protein kinase

MKP:

MAPK phosphatase

MPB:

3-(N-maleimido-propionyl)biocytin

MRM:

Multiple reaction monitoring

NEM:

N-ethylmaleimide

NF-κB:

Nuclear factor-κB

NOX:

NADPH oxidase

NRPTP:

Non-receptor PTP

O2 • − :

Superoxide anion

oxPTP Ab:

Oxidized PTP active site antibody

PD:

Pull down

PDGF:

Platelet-derived growth factor

PI3K:

Phosphatidylinositol 3-kinase

PKC:

Protein kinase C

PROP:

Purification of reversibly oxidized proteins

PRX:

Peroxiredoxin

PTK:

Protein-tyrosine kinase

PTP:

Protein-tyrosine phosphatase

PTP1B-OX:

Oxidized form of PTP1B

PV:

Pervanadate

PVSN-N3 :

4-(Azidomethyl)phenyl ethenesulfonate azide

ROS:

Reactive oxygen species

RTK:

Receptor tyrosine kinase

S :

Thiolate

scFv:

Single-chain variable fragment

SO2H:

Sulfinic acid

SO3H:

Sulfonic acid

SOD:

Superoxide dismutase

SOH:

Sulfenic acid

T2DM:

Type 2 diabetes mellitus

TCA:

Trichloroacetic acid

TCEP:

Tris(2-carboxyethyl)phosphine

TNF-α:

Tumor necrosis factor-α

TRX:

Thioredoxin

VEGF:

Vascular endothelial growth factor

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Xu, Y., Neel, B.G. (2013). Redox Regulation of PTPs in Metabolism: Focus on Assays. In: Bence, K. (eds) Protein Tyrosine Phosphatase Control of Metabolism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7855-3_1

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