Protein Tyrosine Phosphatase 1B Is a Novel Regulator of Central Brain-Derived Neurotrophic Factor and Tropomyosin Receptor Kinase B Signaling [Metabolism]
October 6th, 2014 by Ozek, C., Kanoski, S. E., Zhang, Z.-Y., Grill, H. J., Bence, K. K.
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, hypothalami from 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.