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

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.
Mesh Terms:
Animals, Brain-Derived Neurotrophic Factor, Cell Line, Tumor, Gene Expression Regulation, Enzymologic, Humans, Hypothalamus, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons, Phosphorylation, Protein Binding, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Protein-Tyrosine Kinases, Receptor, trkB, Signal Transduction, Temperature
J. Biol. Chem.
Date: Nov. 14, 2014
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