The trkB tyrosine protein kinase gene is closely related to the trk proto-oncogene, which encodes a receptor for nerve growth factor (NGF) and neurotrophin-3 (NT-3). trkB is expressed in structures of the central and peripheral nervous systems, suggesting it may also encode a receptor for neurotrophic factors. This study shows that brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation of gp145 trkB, a receptor encoded by trkB. BDNF and NT-3 can induce DNA synthesis in quiescent NIH 3T3 cells expressing gp145 trkB. Cotransfection of plasmids encoding gp145 trkB and BDNF or NT-3 leads to transformation of recipient NIH 3T3 cells. BDNF elicits a response at least two orders of magnitude higher than NT-3. Additionally, 125I-NT-3 binds to NIH 3T3 cells expressing gp145 trkB, and this binding can be competed by NT-3 and BDNF but not by NGF. These findings indicate that gp145 trkB may function as a neurotrophic receptor for BDNF and NT-3. The study also shows that BDNF and NT-3 can induce phosphorylation of gp145 trkB receptors and that BDNF has higher mitogenic activity than NT-3. BDNF and NT-3 can induce DNA synthesis in quiescent NIH 3T3 cells expressing gp145 trkB. BDNF binds to gp145 trkB receptors with higher affinity than NT-3. These results confirm that gp145 trkB is a functional receptor for BDNF and NT-3. The study also shows that BDNF and NT-3 are expressed in various neural structures and that their expression is correlated with trkB expression. The findings suggest that gp145 trkB may play a role in the transport and/or clearance of the putative trkB ligand. The study provides evidence that BDNF and NT-3 are neurotrophic factors that bind to trkB receptors and may have roles in the development and function of the nervous system.The trkB tyrosine protein kinase gene is closely related to the trk proto-oncogene, which encodes a receptor for nerve growth factor (NGF) and neurotrophin-3 (NT-3). trkB is expressed in structures of the central and peripheral nervous systems, suggesting it may also encode a receptor for neurotrophic factors. This study shows that brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation of gp145 trkB, a receptor encoded by trkB. BDNF and NT-3 can induce DNA synthesis in quiescent NIH 3T3 cells expressing gp145 trkB. Cotransfection of plasmids encoding gp145 trkB and BDNF or NT-3 leads to transformation of recipient NIH 3T3 cells. BDNF elicits a response at least two orders of magnitude higher than NT-3. Additionally, 125I-NT-3 binds to NIH 3T3 cells expressing gp145 trkB, and this binding can be competed by NT-3 and BDNF but not by NGF. These findings indicate that gp145 trkB may function as a neurotrophic receptor for BDNF and NT-3. The study also shows that BDNF and NT-3 can induce phosphorylation of gp145 trkB receptors and that BDNF has higher mitogenic activity than NT-3. BDNF and NT-3 can induce DNA synthesis in quiescent NIH 3T3 cells expressing gp145 trkB. BDNF binds to gp145 trkB receptors with higher affinity than NT-3. These results confirm that gp145 trkB is a functional receptor for BDNF and NT-3. The study also shows that BDNF and NT-3 are expressed in various neural structures and that their expression is correlated with trkB expression. The findings suggest that gp145 trkB may play a role in the transport and/or clearance of the putative trkB ligand. The study provides evidence that BDNF and NT-3 are neurotrophic factors that bind to trkB receptors and may have roles in the development and function of the nervous system.