Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signalling

Nature. 1991 Sep 26;353(6342):361-3. doi: 10.1038/353361a0.


The colony-stimulating factor-1 receptor (CSF-1R) mediates its pleiotropic effects through the coupling of its ligand-activated tyrosine kinase to multiple intracellular effector proteins, whose combined actions determine the magnitude and specificity of the biological response. The interaction of cytoplasmic signalling molecules with CSF-1R is mediated in part by sequence motifs flanking sites of receptor tyrosine phosphorylation. Mutation of an autophosphorylation site at tyrosine 809 in the cytoplasmic domain of human CSF-1R does not significantly reduce its ligand-stimulated tyrosine kinase activity, binding to phosphatidylinositol 3-kinase, or induction of the immediate early response genes, c-fos and junB (ref.2). Unlike cells bearing wild-type receptors, mouse NIH3T3 cells expressing mutant CSF-1R(Phe 809) were unable to grow in serum-free medium containing human recombinant CSF-1 and did not form colonies in semi-solid medium in its presence. CSF-1 induction of c-myc messenger RNA in these cells was impaired, but enforced expression of an exogenous c-myc gene restored their ability to proliferate in response to the growth factor. These studies demonstrate a receptor-mediated bifurcation of intracellular signal transduction pathways during the immediate early response and assign a central role for c-myc in CSF-1-induced mitogenesis.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Division / genetics
  • Cell Line
  • Gene Expression Regulation / physiology
  • Genes, myc / physiology*
  • Genetic Vectors
  • Humans
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Mutation
  • Receptor, Macrophage Colony-Stimulating Factor / genetics*
  • Receptor, Macrophage Colony-Stimulating Factor / physiology
  • Retroviridae
  • Signal Transduction / genetics
  • Signal Transduction / physiology


  • Macrophage Colony-Stimulating Factor
  • Receptor, Macrophage Colony-Stimulating Factor