| First Author | Ozek C | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 46 | Pages | 31682-92 |
| PubMed ID | 25288805 | Mgi Jnum | J:218302 |
| Mgi Id | MGI:5617132 | Doi | 10.1074/jbc.M114.603621 |
| Citation | Ozek C, et al. (2014) Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling. J Biol Chem 289(46):31682-92 |
| abstractText | 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. |
