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Protein-Tyrosine Phosphatase 1B Substrates and Control of Metabolism

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Protein Tyrosine Phosphatase Control of Metabolism

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Abstract

Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of several signaling networks that are implicated in human metabolic diseases such as diabetes and obesity. A growing body of evidence demonstrates that PTP1B displays exquisite substrate specificity. In this chapter we review mechanisms that regulate PTP1B–susbtrate interactions and highlight substrates that mediate PTP1B metabolic actions. PTP1B–substrate interactions are modulated by PTP1B subcellular location and numerous posttranslational modifications that regulate its activity such as oxidation, nitrosylation, sulfhydration, sumoylation, phosphorylation, and proteolysis. The metabolic actions of PTP1B are mediated by key physiological substrates that regulate insulin and leptin signaling, cell–cell communication, and endoplasmic reticulum (ER) stress response.

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Abbreviations

ER:

Endoplasmic reticulum

AMPK:

AMP-activated protein kinase

ASO:

Antisense oligonucleotide

ATF6:

Activating transcription factor 6

BRET:

Bioluminescence resonance energy transfer

EGFR:

Epidermal growth factor receptor

eIF2α:

Eukaryotic translation initiation factor 2α

ERK:

Extracellular signal-regulated kinase

FRET:

Fluorescence resonance energy transfer

Gab:

Grb2-associated binder

GH:

Growth hormone

H2S:

Hydrogen sulfide

HFD:

High fat diet

INM:

Inner nuclear membrane

IR:

Insulin receptor

IRE1α:

Inositol requiring enzyme 1α

IRS:

Insulin receptor substrate

JAK:

Janus kinase

KO:

Knockout

LepR:

Leptin receptor

MVB:

Multivesicular bodies

NO:

Nitric oxide

PDGFR:

Platelet-derived growth factor receptor

PERK:

PKR-like ER-resident kinase

PI3K:

Phosphatidylinositol 3-kinase

PIAS:

Protein inhibitor of activated STAT1

PM:

Plasma membrane

POMC:

Pro-opiomelanocortin

PPARγ:

Peroxisome proliferator-activated receptor γ

PTP1B:

Protein-tyrosine phosphatase 1B

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RTK:

Receptor tyrosine kinase

SH:

Src homology

STAT:

Signal transducer and activator of transcription

SUMO:

Small ubiquitin-like modifier

UPR:

Unfolded protein response

XBP1:

X-box binding protein 1

ZO1:

Zonula occludens 1

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Authors and Affiliations

  1. Department of Nutrition, University of California Davis, Davis, CA, 95616, USA

    Yannan Xi B.Sc. & Fawaz G. Haj M.Sc., D.Phil.

  2. Department of Internal Medicine, University of California Davis, Sacramento, CA, 95817, USA

    Fawaz G. Haj M.Sc., D.Phil.

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  1. Yannan Xi B.Sc.
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  2. Fawaz G. Haj M.Sc., D.Phil.
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Correspondence to Fawaz G. Haj M.Sc., D.Phil. .

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  1. Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Kendra K. Bence

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Xi, Y., Haj, F.G. (2013). Protein-Tyrosine Phosphatase 1B Substrates and Control of Metabolism. In: Bence, K. (eds) Protein Tyrosine Phosphatase Control of Metabolism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7855-3_3

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