Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling

Ceren Ozek, Scott E. Kanoski, Zhong Yin Zhang, Harvey J. Grill, Kendra K. Bence

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Neuronal protein-tyrosine phosphatase 1B (PTP1B) deficiency in mice results in enhanced leptin signaling and protection from diet-induced obesity; however, whether additional signaling pathways in the brain contribute to the metabolic effects of PTP1B deficiency remains unclear. Here, we show that the tropomyosin receptor kinase B (TrkB) receptor is a direct PTP1B substrate and implicate PTP1B in the regulation of the central brain-derived neurotrophic factor (BDNF) signaling. PTP1B interacts with activated TrkB receptor in mouse brain and human SH-SY5Y neuroblastoma cells. PTP1B overexpression reduces TrkB phosphorylation and activation of downstream signaling pathways, whereas PTP1B inhibition augments TrkB signaling. Notably, brains of Ptpn1-/- mice exhibit enhanced TrkB phosphorylation, and Ptpn1-/- mice are hypersensitive to central BDNF-induced increase in core temperature. Taken together, our findings demonstrate that PTP1B is a novel physiological regulator of TrkB and that enhanced BDNF/TrkB signaling may contribute to the beneficial metabolic effects of PTP1B deficiency.

Original languageEnglish (US)
Pages (from-to)31682-31692
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number46
DOIs
StatePublished - Nov 14 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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