TY - JOUR
T1 - The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase
AU - Varticovski, Lyuba
AU - Druker, Brian
AU - Morrison, Deborah
AU - Cantley, Lewis
AU - Roberts, Thomas
PY - 1989
Y1 - 1989
N2 - 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.
AB - 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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U2 - 10.1038/342699a0
DO - 10.1038/342699a0
M3 - Article
C2 - 2556641
AN - SCOPUS:0024372679
SN - 0028-0836
VL - 342
SP - 699
EP - 702
JO - Nature
JF - Nature
IS - 6250
ER -