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Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress

Feng Gu1, Duc Thang Nguyên, Matthew Stuible

  • 1McGill Cancer Centre and Department of Biochemistry, Montreal, Quebec H3G 1Y6, Canada.

The Journal of Biological Chemistry
|October 7, 2004
PubMed

Insights

Protein-tyrosine phosphatase 1B (PTP-1B) regulates the endoplasmic reticulum unfolded protein response. Its absence impairs ER stress signaling, including IRE1 pathways, JNK activation, and apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein-tyrosine phosphatase 1B (PTP-1B) is a key regulator of insulin signaling and metabolism.
  • Its role in dephosphorylating cell surface receptor tyrosine kinases is known, but its function within the endoplasmic reticulum (ER) is unclear.

Purpose of the Study:

  • To investigate the role of PTP-1B in modulating receptor function from the ER.
  • To determine if PTP-1B plays a role in the unfolded protein response (UPR) within the ER.

Main Methods:

  • Utilized PTP-1B knock-out mouse embryonic fibroblasts.
  • Exposed cells to ER stressors: tunicamycin and azetidine-2 carboxylic acid.
  • Assessed IRE1 signaling pathway components, including JNK activation, XBP-1 splicing, EDEM gene induction, and ER stress-induced apoptosis.

Main Results:

  • Absence of PTP-1B led to impaired ER stress-induced IRE1 signaling.
  • JNK activation, XBP-1 splicing, and EDEM gene induction were attenuated in PTP-1B deficient cells.
  • ER stress-induced apoptosis was reduced in the absence of PTP-1B.

Conclusions:

  • PTP-1B is not merely a passive ER resident; it actively potentiates IRE1-mediated ER stress signaling.
  • PTP-1B plays an essential function in regulating the unfolded protein response in the ER compartment.
  • These findings reveal a novel role for PTP-1B in cellular stress response pathways.

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