Ectopic expression of a chimeric colony-stimulating Factor-1/TrkB-receptor promotes CSF-1-dependent survival of cultured sympathetic neurons Academic Article uri icon

Overview

MeSH Major

  • Receptor Protein-Tyrosine Kinases
  • Receptor, Macrophage Colony-Stimulating Factor
  • Receptors, Nerve Growth Factor

abstract

  • The regulation of the density of innervation and the promotion of survival of neurons are the original effects depending on neurotrophins. Here we analyse such effects evoked by trkB tyrosine kinase in transfected PC12 cells and transfected sympathetic neurons. In order to exclude the previously described modulation of trk kinase activity by the extracellular activation of the low-affinity p75 neurotrophin receptor, we applied a chimeric receptor approach: The extracellular domain of colony-stimulating factor-1 (CSF-1) receptor was fused to the transmembrane and cytoplasmic domain of the trkB tyrosine kinase receptor, allowing its selective activation by the heterologous ligand. Protein expression and CSF-1-induced tyrosine phosphorylation of the chimeric receptor protein was demonstrated in transfected COS cells. After stable transfection into nerve growth factor (NGF)-responsive PC12 cells, CSF-1 mediated the K252a-sensitive induction of fiber outgrowth. Furthermore, we were able to show by heterologous expression of the chimeric receptor, that activation of trkB tyrosine kinase activity is sufficient to promote survival of neurotrophin deprived sympathetic neurons.

publication date

  • August 28, 1998

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1998.9219

PubMed ID

  • 9731232

Additional Document Info

start page

  • 891

end page

  • 7

volume

  • 249

number

  • 3