trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor.
A variety of findings seem to functionally link brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), while distinguishing both of these factors from the third member of the neurotrophin family, nerve growth factor (NGF). Here we demonstrate that all three of these neuronal survival molecules bind similarly to the low affinity NGF receptor, but that BDNF and NT-3, unlike NGF, do not act via the high affinity NGF receptor. However, both BDNF and NT-3, but not NGF, bind to full-length and truncated forms of a receptor-like tyrosine kinase, trkB, for which no ligand had previously been identified. In addition to binding BDNF and NT-3, trkB can mediate functional responses to both of these neurotrophins when it is expressed in PC12 cells, although BDNF appears to be the more effective ligand. Thus trkB encodes an essential component of a functional receptor for BDNF and NT-3, but not for NGF. Further evidence predicts the existence of additional functional receptors for the neurotrophins.
Squinto
Stephen P
SP
Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, New York 10591, USA.
Stitt
Trevor N
TN
Aldrich
Thomas H
TH
Davis
Samuel
S
Blanco
Stella M
SM
RadzieJewski
Czeslaw
C
Glass
David J
DJ
Masiakowski
Piotr
P
Furth
Mark E
ME
Valenzuela
David M
DM
Distefano
Peter S
PS
Yancopoulos
George D
GD
D000310:Adrenal Gland Neoplasms; D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D019208:Brain-Derived Neurotrophic Factor; D002460:Cell Line; D003432:Cross-Linking Reagents; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020933:Neurotrophin 3; D010673:Pheochromocytoma; D011485:Protein Binding; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D003432:Cross-Linking Reagents; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011956:Receptors, Cell Surface; D012313:RNA