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

Abstract

THE colony-stimulating factor-1 receptor (CSF-1 R) 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-1 R is mediated in part by sequence motifs flanking sites of receptor tyrosine phosphorylation1. 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-lR(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.

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Roussel, M., Cleveland, J., Shurtleff, S. et al. Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signalling. Nature 353, 361–363 (1991). https://doi.org/10.1038/353361a0

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