COLONY stimulating f actor-1 (CSF-1) is a lineage-specific growth factor required for proliferation and survival of mononuclear phagocytes and their precursors. The CSF-1 receptor belongs to a family of ligand-activated protein-tyrosine kinases. Activation of the platelet-derived growth factor receptor, but not the CSF-1 receptor, leads to an increase in phospholipase C activity and a subsequent elevation in intracellular calcium. Recent studies have shown that a novel phosphoinositol (Ptdlns) kinase, termed Ptdlns-3 kinase, is stimulated by the platelet-derived growth factor receptor and certain oncogenes in the protein-tyrosine kinase family. PtdIns-3 kinase phosphorylates the D-3 hydroxyl position of the inositol ring of Ptdlns, and its products do not participate in the generation of the second messenger inositol 1,4,5-trisphosphate (Ins(l,4,5)P3). Here we report that addition of CSF-1 is followed by activation of PtdIns-3 kinase in a macrophage cell line (P388 Dl), which contains CSF-1 receptors, and in BALB/c fibro-blasts made to express the human CSF-1 receptor. Furthermore, we show that activation of the CSF-1 receptor results in the accumulation in intact cells of polyphosphoinositides phosphory-lated at the D-3 position of the inositol ring. Thus activation of the CSF-1 receptor stimulates PtdIns-3 kinase activity, indicating a novel pathway for CSF-1 receptor-mediated signal transduction.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Stanley, E. R. & Jubinsky, P. T. Clin. Haemat. 13, 329–348 (1984).
Guilbert, L. J. & Stanley, E. R. J. biol. Chem. 261, 4024–4032 (1986).
Guilbert, L. J. Tynan, P. W. & Stanley, E. R. J. cell. Biochem. 31, 203–216 (1986).
Habenicht, A. J. R. et al., J. Biol. Chem. 256, 12329–12235 (1981).
Berridge, M. Heslop J. Irvine R. F. & Brown, K. D. Biochem. J. 222, 195–201 (1984).
Whetton, A. D. Monk P. N. Consalvey, S. D. & Downes, C. P. EMBO J. 5, 3281–3286 (1986).
Whitman, M. Kaplan, D. Roberts, T. & Cantley, L. Biochem. J. 247, 165–174 (1987).
Kaplan D. R. et al. Cell 50, 1021–1029 (1987).
Whitman, M. Kaplan, D. R. Schaffhausen, B. Cantley, L. and Roberts, T. Nature 315, 239–242 (1985).
Varticovski, L. & Cantley, L. Blood 72, 232a (1988).
Auger, K. R. Serunian, L. A. Soltoff, S. P. Libby, P. & Cantley, L. Cell 57, 167–175 (1989).
Whitman, M. Downs, C. P. Keeler, M. Keller, T. & Cantley, L. Nature 332, 644–646 (1988).
Morrison, D. K. Browning, P. White, M. & Roberts, T. Molec. cell. Biol. 8, 176–185 (1988).
Piwnika-Worms, H. Saunders, K. B. Roberts, T. M. Smith, A. E. & Cheng, S. H. Cell 49, 75–82 (1987).
Das, S. K. Stanley, R. E. Guilbert, L. J. & Forman, L. W. J. cell. Physiol. 104, 359–364 (1980).
Russel, M. F. et al. Nature 325, 549–552 (1987).
Rousel, M. F. Downing, J. R. Rettenmier, C. W. & Sherr, C. J. Cell 55, 979–986 (1988).
Stanley, E. R. & Guilbert, L. J. J. immunol. Meth. 42, 253–284 (1981).
Morgan, C. Pollard, J. W. & Stanley, R. J. cell. Physiol. 130, 420–427 (1987).
Fukui, Y. & Hanafusa, H. Molec. cell. Biol. 9, 1651–1658 (1989).
Coughlin, S. R. Escobedo, J. A. & Williams, L. T. Science 243, 1191–1193 (1989).
Williams, L. T. Science 243, 1564–1570 (1989).
Morgan, W. C. Kaplan, D. R. Pallas, D. C. & Roberts, T. M. J. Virol. 62, 3407–3411 (1988).
Frackleton, A. R. Jr, Ross, A. H. & Eisen, N. H. Molec cell. Biol. 3, 1343–1352 (1983).
About this article
Cite this article
Varticovski, L., Druker, B., Morrison, D. et al. The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase. Nature 342, 699–702 (1989). https://doi.org/10.1038/342699a0
ACS Synthetic Biology (2017)
Cell Research (2014)
CpG- and LPS-activated MAPK signaling in in vitro cultured salmon (Salmo salar) mononuclear phagocytes
Fish & Shellfish Immunology (2013)
Cellular and Molecular Life Sciences (2013)
PI3K p110γ Deletion Attenuates Murine Atherosclerosis by Reducing Macrophage Proliferation but Not Polarization or Apoptosis in Lesions
PLoS ONE (2013)