The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3

TrkB is a tyrosine protein kinase gene highly related to Trk, a proto-oncogene that encodes a receptor for nerve growth factor (NGF) and Neurotrophin-3 (NT-3). TrkB expression is confined to structures of the central and peripheral nervous systems, suggesting it also encodes a receptor for Neurotrophic Factors. Here we show that brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation on tyrosine of gp145trkB, one of the receptors encoded by TrkB. BDNF and NT-3 can induce DNA synthesis in quiescent NIH 3T3 cells that express gp145trkB. Cotransfection of plasmids encoding gp145trkB and BDNF or NT-3 leads to transformation of recipient NIH 3T3 cells. In these assays, BDNF elicits a response at least two orders of magnitude higher than NT-3. Finally, 125I-NT-3 binds to NIH 3T3 cells expressing gp145trkB; binding can be competed by NT-3 and BDNF but not by NGF. These findings indicate that gp145trkB may function as a neurotrophic receptor for BDNF and NT-3.