The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase

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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References

  1. 1

    Stanley, E. R. & Jubinsky, P. T. Clin. Haemat. 13, 329–348 (1984).

    CAS  PubMed  Google Scholar 

  2. 2

    Guilbert, L. J. & Stanley, E. R. J. biol. Chem. 261, 4024–4032 (1986).

    CAS  PubMed  Google Scholar 

  3. 3

    Guilbert, L. J. Tynan, P. W. & Stanley, E. R. J. cell. Biochem. 31, 203–216 (1986).

    CAS  Article  Google Scholar 

  4. 4

    Habenicht, A. J. R. et al., J. Biol. Chem. 256, 12329–12235 (1981).

    CAS  PubMed  Google Scholar 

  5. 5

    Berridge, M. Heslop J. Irvine R. F. & Brown, K. D. Biochem. J. 222, 195–201 (1984).

    CAS  Article  Google Scholar 

  6. 6

    Whetton, A. D. Monk P. N. Consalvey, S. D. & Downes, C. P. EMBO J. 5, 3281–3286 (1986).

    CAS  Article  Google Scholar 

  7. 7

    Whitman, M. Kaplan, D. Roberts, T. & Cantley, L. Biochem. J. 247, 165–174 (1987).

    CAS  Article  Google Scholar 

  8. 8

    Kaplan D. R. et al. Cell 50, 1021–1029 (1987).

    CAS  Article  Google Scholar 

  9. 9

    Whitman, M. Kaplan, D. R. Schaffhausen, B. Cantley, L. and Roberts, T. Nature 315, 239–242 (1985).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Varticovski, L. & Cantley, L. Blood 72, 232a (1988).

    Google Scholar 

  11. 11

    Auger, K. R. Serunian, L. A. Soltoff, S. P. Libby, P. & Cantley, L. Cell 57, 167–175 (1989).

    CAS  Article  Google Scholar 

  12. 12

    Whitman, M. Downs, C. P. Keeler, M. Keller, T. & Cantley, L. Nature 332, 644–646 (1988).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Morrison, D. K. Browning, P. White, M. & Roberts, T. Molec. cell. Biol. 8, 176–185 (1988).

    CAS  Article  Google Scholar 

  14. 14

    Piwnika-Worms, H. Saunders, K. B. Roberts, T. M. Smith, A. E. & Cheng, S. H. Cell 49, 75–82 (1987).

    Article  Google Scholar 

  15. 15

    Das, S. K. Stanley, R. E. Guilbert, L. J. & Forman, L. W. J. cell. Physiol. 104, 359–364 (1980).

    CAS  Article  Google Scholar 

  16. 16

    Russel, M. F. et al. Nature 325, 549–552 (1987).

    ADS  Article  Google Scholar 

  17. 17

    Rousel, M. F. Downing, J. R. Rettenmier, C. W. & Sherr, C. J. Cell 55, 979–986 (1988).

    Article  Google Scholar 

  18. 18

    Stanley, E. R. & Guilbert, L. J. J. immunol. Meth. 42, 253–284 (1981).

    CAS  Article  Google Scholar 

  19. 19

    Morgan, C. Pollard, J. W. & Stanley, R. J. cell. Physiol. 130, 420–427 (1987).

    CAS  Article  Google Scholar 

  20. 20

    Fukui, Y. & Hanafusa, H. Molec. cell. Biol. 9, 1651–1658 (1989).

    CAS  Article  Google Scholar 

  21. 21

    Coughlin, S. R. Escobedo, J. A. & Williams, L. T. Science 243, 1191–1193 (1989).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Williams, L. T. Science 243, 1564–1570 (1989).

    ADS  CAS  Article  Google Scholar 

  23. 23

    Morgan, W. C. Kaplan, D. R. Pallas, D. C. & Roberts, T. M. J. Virol. 62, 3407–3411 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Frackleton, A. R. Jr, Ross, A. H. & Eisen, N. H. Molec cell. Biol. 3, 1343–1352 (1983).

    Article  Google Scholar 

Download references

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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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