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Protein tyrosine phosphatase epsilonC selectively inhibits interleukin-6- and interleukin- 10-induced JAK-STAT

N Tanuma1, H Shima, K Nakamura

  • 1Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.

Blood
|November 8, 2001
PubMed

Insights

Protein tyrosine phosphatase epsilon (PTPepsilonC) inhibits interleukin-6 (IL-6) and interleukin-10 (IL-10) signaling pathways. This cytosolic PTPepsilon isoform selectively suppresses STAT3 phosphorylation, impacting JAK-STAT signaling.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Immunology

Background:

  • Protein tyrosine phosphatase epsilon (PTPepsilon) has cytosolic (PTPepsilonC) and other isoforms.
  • PTPepsilonC has been reported to inhibit interleukin-6 (IL-6) signaling pathways.

Purpose of the Study:

  • To characterize the inhibitory action of PTPepsilonC on IL-6 signaling.
  • To investigate the independence of PTPepsilonC activity from other negative regulators.
  • To analyze the selectivity of PTPepsilonC action toward various cytokines.

Main Methods:

  • Overexpression of PTPepsilonC and its catalytically inactive mutant (PTPepsilonC-DA) in murine M1 myeloid cells.
  • Stimulation with cytokines like IL-6, IL-10, interferon-beta, and interferon-gamma.
  • Analysis of Janus kinase (JAK) activation and STAT (Signal transducer and activator of transcription) protein tyrosine phosphorylation and signaling.

Main Results:

  • PTPepsilonC inhibits IL-6-induced STAT3 tyrosine phosphorylation and signaling independently of SHP-2 and SOCS proteins.
  • Catalytically inactive PTPepsilonC-DA enhances IL-6-induced STAT3 phosphorylation onset and STAT1 activation.
  • PTPepsilonC selectively inhibits IL-6 and IL-10 induced STAT3 tyrosine phosphorylation but not that induced by interferons.

Conclusions:

  • PTPepsilonC acts as a specific negative regulator of IL-6 and IL-10 signaling pathways.
  • The inhibitory mechanism of PTPepsilonC differs from other negative regulators like SHP-2 and SOCS.
  • PTPepsilonC's distinct actions on STAT phosphorylation suggest complex regulatory roles in cytokine signaling.

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