Protein-tyrosine Phosphatase 1B Potentiates IRE1 Signaling during Endoplasmic Reticulum Stress

Gu, Feng; Nguyen, Doan Trang; Stuible, Matthew; Dubé, Nadia; Tremblay, Michel L.; Chevet, Éric

doi:10.1074/jbc.c400261200

Cited by 191 publications

(151 citation statements)

References 29 publications

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“…Fibroblasts from PTP1B-null mice are also resistant to ER-mediated stress (65). In this process, decreased levels of phosphorylated JNK and p38 MAPK correlated with protection (65).…”

Section: Discussionmentioning

confidence: 99%

Protein-tyrosine Phosphatase 1B Deficiency Protects against Fas-induced Hepatic Failure

Sangwan

Paliouras

Cheng

et al. 2006

Journal of Biological Chemistry

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Genetic disruption of protein-tyrosine phosphatase 1B (PTP1B) in mice leads to increased insulin sensitivity and resistance to weight gain. Although PTP1B has been implicated as a regulator of multiple signals, its function in other physiological responses in vivo is poorly understood. Here we demonstrate that PTP1B-null mice are resistant to Fas-induced liver damage and lethality, as evident by reduced hepatic apoptosis in PTP1B-null versus wild type mice and reduced levels of circulating liver enzymes. Activation of pro-apoptotic caspases-8, -9, -3, and -6 was attenuated in livers from PTP1B-null mice following Fas receptor stimulation, although components of the death-inducing signaling complex were intact. Activation of anti-apoptotic regulators, such as the hepatocyte growth factor/Met receptor tyrosine kinase, as well as Raf, ERK1/2, FLIP L , and the NF-B pathway, was elevated in response to Fas activation in livers from PTP1B-null mice. Using PTP1B-deficient primary hepatocytes, we show that resistance to Fas-mediated apoptosis is cell autonomous and that signals involving the Met, ERK1/2, and NF-B pathways are required for cytoprotection. This study identifies a previously unknown physiological role for PTP1B in Fas-mediated liver damage and points to PTP1B as a potential therapeutic target against hepatotoxic agents.

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“…Fibroblasts from PTP1B-null mice are also resistant to ER-mediated stress (65). In this process, decreased levels of phosphorylated JNK and p38 MAPK correlated with protection (65).…”

Section: Discussionmentioning

confidence: 99%

Protein-tyrosine Phosphatase 1B Deficiency Protects against Fas-induced Hepatic Failure

Sangwan

Paliouras

Cheng

et al. 2006

Journal of Biological Chemistry

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“…In addition, we do not exclude the possibility that these PTPs regulate IRE1␣ and/or ATF6 arms of the ER stress response. Indeed, the absence of PTP1B in fibroblasts leads to impaired ER stressinduced IRE1␣ signaling in fibroblasts (21).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, PTP1B has been reported to regulate ER stress signaling. Mouse embryonic fibroblasts lacking PTP1B exhibit impaired IRE1␣ signaling and attenuated ER stress-induced apoptosis (21), whereas liver-specific PTP1B deficiency protects mice against HFD-induced ER stress (22). In this study, we determined the role of PTP1B and TCPTP in ER stress signaling in ␤ cells.…”

mentioning

confidence: 99%

Differential Regulation of Endoplasmic Reticulum Stress by Protein Tyrosine Phosphatase 1B and T Cell Protein Tyrosine Phosphatase

Bettaieb

Liu

et al. 2011

Journal of Biological Chemistry

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Protein-tyrosine phosphatase 1B (PTP1B) and T cell proteintyrosine phosphatase (TCPTP) are closely related intracellular phosphatases implicated in the control of glucose homeostasis. PTP1B and TCPTP can function coordinately to regulate protein tyrosine kinase signaling, and PTP1B has been implicated previously in the regulation of endoplasmic reticulum (ER) stress. In this study, we assessed the roles of PTP1B and TCPTP in regulating ER stress in the endocrine pancreas. PTP1B and TCPTP expression was determined in pancreases from chow and high fat fed mice and the impact of PTP1B and TCPTP overor underexpression on palmitate-or tunicamycin-induced ER stress signaling assessed in MIN6 insulinoma ␤ cells. PTP1B expression was increased, and TCPTP expression decreased in pancreases of mice fed a high fat diet, as well as in MIN6 cells treated with palmitate. PTP1B overexpression or TCPTP knockdown in MIN6 cells mitigated palmitate-or tunicamycininduced PERK/eIF2␣ ER stress signaling, whereas PTP1B deficiency enhanced ER stress. Moreover, PTP1B deficiency increased ER stress-induced cell death, whereas TCPTP deficiency protected MIN6 cells from ER stress-induced death. ER stress coincided with the inhibition of Src family kinases (SFKs), which was exacerbated by PTP1B overexpression and largely prevented by TCPTP knockdown. Pharmacological inhibition of SFKs ameliorated the protective effect of TCPTP deficiency on ER stress-induced cell death. These results demonstrate that PTP1B and TCPTP play nonredundant roles in modulating ER stress in pancreatic ␤ cells and suggest that changes in PTP1B and TCPTP expression may serve as an adaptive response for the mitigation of chronic ER stress.

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“…Enfin, dans des cellules déficientes pour la protéine phosphatase PTP1B, l'épissage de XBP1 ainsi que la phosphorylation de JNK sont diminués. Ces cellules sont également plus résistantes à l'apoptose induite lors d'un stress du RE [33].…”

Section: Gènes Cibles Xbp1unclassified

Stress du réticulum endoplasmique

Bouchecareilh

Chevet

2009

Med Sci (Paris)

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Protein-tyrosine Phosphatase 1B Potentiates IRE1 Signaling during Endoplasmic Reticulum Stress

Cited by 191 publications

References 29 publications

Protein-tyrosine Phosphatase 1B Deficiency Protects against Fas-induced Hepatic Failure

Protein-tyrosine Phosphatase 1B Deficiency Protects against Fas-induced Hepatic Failure

Differential Regulation of Endoplasmic Reticulum Stress by Protein Tyrosine Phosphatase 1B and T Cell Protein Tyrosine Phosphatase

Stress du réticulum endoplasmique

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