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.
Klein
R
R
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Nanduri
V
V
Jing
S A
SA
Lamballe
F
F
Tapley
P
P
Bryant
S
S
Cordon-Cardo
C
C
Jones
K R
KR
Reichardt
L F
LF
Barbacid
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology*; D020933:Neurotrophin 3; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020813:Receptor, trkB; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; C064371:Ntrk2 protein, mouse; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB