The trkB Tyrosine Protein Kinase Is a Receptor for Brain-Derived Neurotrophic Factor and neurotrophin-3

Cell. 1991 Jul 26;66(2):395-403. doi: 10.1016/0092-8674(91)90628-c.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor
  • Cell Division / drug effects
  • Cell Line
  • Kinetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / pharmacology*
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / pharmacology*
  • Neurotrophin 3
  • Plasmids
  • Protein-Tyrosine Kinases / metabolism*
  • Receptor, trkB
  • Receptors, Cell Surface / metabolism*
  • Receptors, Nerve Growth Factor
  • Transfection

Substances

  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neurotrophin 3
  • Receptors, Cell Surface
  • Receptors, Nerve Growth Factor
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases
  • Receptor, trkB