The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase (original) (raw)

Nature volume 342, pages 699–702 (1989)Cite this article

Abstract

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.

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Author notes

  1. Deborah Morrison
    Present address: Department of Medicine, Howard Hughes Medical Institute, University California, San Francisco, California, 94143, USA

Authors and Affiliations

  1. Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA
    Lyuba Varticovski & Lewis Cantley
  2. Dana-Farber Cancer Institute, Boston, Massachusetts, 02135, USA
    Brian Druker, Deborah Morrison & Thomas Roberts

Authors

  1. Lyuba Varticovski
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  2. Brian Druker
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  3. Deborah Morrison
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  4. Lewis Cantley
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  5. Thomas Roberts
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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

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