PTP1B in the Periphery: Regulating Insulin Sensitivity and ER Stress



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.


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.



Activating transcription factor 4


Activating transcription factor 6


Binding immunoglobulinprotein


CAAT/enhancer-binding protein homologous protein


ER degradation-enhancing α-mannosidase-like protein


Translation initiation factor 2α


Endoplasmic reticulum stress


ER-associated degradation


ER-localized DnaJ homologue


Growth arrest and DNA damage 34


Glucose-regulated protein 94


Glycogen synthase kinase 3


Insulin receptor


Inositol-requiring enzyme 1


Insulin receptor substrate


Mammalian target of rapamycin


PKR-like ER kinase


Phosphatidylinositol 3-kinase


Protein kinase B


Protein tyrosine phosphatase 1B


Unfolded protein response


X box-binding protein 1



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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Institute of Medical SciencesUniversity of AberdeenAberdeenUK

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