Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase

Ahmed Bettaieb, Siming Liu, Yannan Xi, Naoto Nagata, Kosuke Matsuo, Izumi Matsuo, Samah Chahed, Jesse Bakke, Heike Keilhack, Tony Tiganis, Fawaz Haj

Research output: Contribution to journalArticle

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Abstract

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 andTCPTPoveror underexpression on palmitate- or tunicamycin-induced ER stress signaling assessed in MIN6 insulinoma β 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 tunicamycin-induced PERK/eIF2α 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 β cells and suggest that changes in PTP1B and TCPTP expression may serve as an adaptive response for the mitigation of chronic ER stress.

Original languageEnglish (US)
Pages (from-to)9225-9235
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number11
DOIs
StatePublished - Mar 18 2011

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Non-Receptor Type 2 Protein Tyrosine Phosphatase
Non-Receptor Type 1 Protein Tyrosine Phosphatase
Endoplasmic Reticulum Stress
Heat-Shock Proteins
T-cells
Phosphoric Monoester Hydrolases
T-Lymphocytes
Palmitates
Tunicamycin
src-Family Kinases
Cell death
protein phosphatase-T
Pancreas
Cell Death
Fats
Insulinoma

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase. / Bettaieb, Ahmed; Liu, Siming; Xi, Yannan; Nagata, Naoto; Matsuo, Kosuke; Matsuo, Izumi; Chahed, Samah; Bakke, Jesse; Keilhack, Heike; Tiganis, Tony; Haj, Fawaz.

In: Journal of Biological Chemistry, Vol. 286, No. 11, 18.03.2011, p. 9225-9235.

Research output: Contribution to journalArticle

Bettaieb, A, Liu, S, Xi, Y, Nagata, N, Matsuo, K, Matsuo, I, Chahed, S, Bakke, J, Keilhack, H, Tiganis, T & Haj, F 2011, 'Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase', Journal of Biological Chemistry, vol. 286, no. 11, pp. 9225-9235. https://doi.org/10.1074/jbc.M110.186148
Bettaieb, Ahmed ; Liu, Siming ; Xi, Yannan ; Nagata, Naoto ; Matsuo, Kosuke ; Matsuo, Izumi ; Chahed, Samah ; Bakke, Jesse ; Keilhack, Heike ; Tiganis, Tony ; Haj, Fawaz. / Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 11. pp. 9225-9235.
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AU - Matsuo, Kosuke

AU - Matsuo, Izumi

AU - Chahed, Samah

AU - Bakke, Jesse

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