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Distinct PI(3)Ks mediate mitogenic signalling and cell migration in macrophages

Nature Cell Biology volume 1, pages 69–71 (1999)Cite this article

We used western blotting and immunoprecipitation techniques to show that antibodies raised against p110α, β or δ peptides were specific to each isoform (see Methods). Antibodies against the carboxy termini of p110s selectively neutralized the lipid-kinase activity of the specific p110 in vitro, whereas neither preimmune IgG nor an antibody against the Ras-binding domain of p110δ (δRBD antibody) blocked lipid-kinase activity of any p110 PI(3)K (Fig. 1b).

The murine macrophage cell line Bac1.2F5 depends on CSF-1 for survival and proliferation, and CSF-1 also stimulates actin reorganization and cell motility 4. Bac1.2F5 cells express p110α, β and δ, which all become recruited to the activated CSF-1 receptor (data not shown). The PI(3)K inhibitor LY294002, which inhibits all p110 isoforms to the same extent 2, inhibited CSF1-stimulated DNA synthesis with a half-maximal inhibitory concentration similar to that reported for class IA PI(3)Ks in other cells (that is, 5–10 µM; ref. 5). LY294002 also blocked CSF1-induced actin reorganization and cell migration (data not shown).

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Figure 1: Effects of specific anti-p110 antibodies on macrophage functions.

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Acknowledgements

We thank R. Garg and H. Drakesmith for help; K. Higashi and L. O'Rourke for help in antibody purification; and J. Backer for p110α antibodies. B.V. is supported in part by the Flemish Fund for Scientific Research, Belgium. W.E.A. was supported by a grant from the Arthritis and Rheumatism Council, UK. G.E.J. acknowledges support from the Wellcome Trust.

Correspondence and requests for materials should be addressed to B.V.

Supplementary Information is available on Nature Cell Biology’s World-Wide Web site (http://www.nature.com/ncb/webfocus/index.html) or as paper copy from the London editorial office of Nature Cell Biology.

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research, University College London Branch, London , W1P 8BT, UK

    Bart Vanhaesebroeck, Carol Sawyer, Claire Wells, Michael D. Waterfield & Anne J. Ridley

  2. The Randall Institute, King's College, London, WC2B 5RL, UK

    Gareth E. Jones, William E. Allen & Daniel Zicha

  3. Ludwig Institute for Cancer Research, Uppsala, 751 24, Sweden

    Roya Hooshmand-Rad

  4. Department of Biochemistry & Molecular Biology, University College London, London, WC1E 6BT, UK

    Michael D. Waterfield & Anne J. Ridley

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Vanhaesebroeck, B., Jones, G., Allen, W. et al. Distinct PI(3)Ks mediate mitogenic signalling and cell migration in macrophages . Nat Cell Biol 1, 69–71 (1999). https://doi.org/10.1038/9045

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