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PTP1B in the Periphery: Regulating Insulin Sensitivity and ER Stress

Chapter

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is a major regulator of body mass and insulin sensitivity and plays an important role in signal transduction of many important metabolic pathways such as insulin, leptin, integrin, growth hormone, and endoplasmic reticulum (ER) stress response signaling. In this article we review current literature on the divergent role of PTP1B in different tissues in ER stress response signal transduction and its control of insulin sensitivity in vivo. Recent evidence suggests that PTP1B is a direct player in the ER stress response pathway potentially due to direct dephosphorylation of PKR-like ER kinase (PERK) on its tyrosine 619 site. Considering that the ER stress response pathway is involved in the pathophysiology of insulin and leptin resistance, aging, neurodegenerative disorders, cancer, and other diseases, it implicates PTP1B inhibitors as a viable therapeutic target in the treatment and/or prevention of a number of these diseases.

Keywords

Endoplasmic Reticulum Stress Insulin Receptor Unfold Protein Response Endoplasmic Reticulum Stress Response Endoplasmic Reticulum Stress Induction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ATF4

Activating transcription factor 4

ATF6

Activating transcription factor 6

BIP

Binding immunoglobulinprotein

CHOP

CAAT/enhancer-binding protein homologous protein

EDEM

ER degradation-enhancing α-mannosidase-like protein

eIF2α

Translation initiation factor 2α

ER

Endoplasmic reticulum stress

ERAD

ER-associated degradation

ERDJ4

ER-localized DnaJ homologue

GADD34

Growth arrest and DNA damage 34

GRP94

Glucose-regulated protein 94

GSK3

Glycogen synthase kinase 3

IR

Insulin receptor

IRE1

Inositol-requiring enzyme 1

IRS

Insulin receptor substrate

mTOR

Mammalian target of rapamycin

PERK

PKR-like ER kinase

PI3K

Phosphatidylinositol 3-kinase

PKB

Protein kinase B

PTP1B

Protein tyrosine phosphatase 1B

UPR

Unfolded protein response

XBP1

X box-binding protein 1

Notes

Acknowledgments

MD is supported by RCUK, British Heart Foundation, Diabetes UK, Tenovus Scotland, European Foundation for the Study of Diabetes (EFSD)/Lilly. NM is the recipient of a British Heart Foundation intermediate basic research fellowship.

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Institute of Medical SciencesUniversity of AberdeenAberdeenUK

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