Calcium mobilization via sphingosine kinase in signalling by the FcɛRI antigen receptor (original) (raw)

Nature volume 380, pages 634–636 (1996)Cite this article

Abstract

CALCIUM mobilization through antigen receptors, including high-affinity IgE receptors (FcsRI), is thought to be mediated by inositol-l,4,5-trisphosphate production (InsP3)1–4. Here we show that antigen clustering of FceRI on the rat mast-cell line (RBL-2H3) activates a sphingosine kinase (SK) and produces sphingo-sine-1-phosphate (SIP), an alternative second messenger for intracellular calcium mobilization. The sphingosine analogue, D-L-_threo_-dihydrosphingosine (DHS), inhibits the SK enzyme competitively with a dissociation constant,_K_i, of 5 to 18 µM. This inhibition substantially suppresses the FceRI-mediated calcium signal, but leaves intact the syk tyrosine kinase activation and the small InsP3 production. The entire InsP3-dependent pathway activated by a transfected G-protein coupled receptor, used here as a positive control, also remained intact. Thus FcsRI principally utilizes a SK pathway to mobilize calcium.

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References

  1. Beaven, M. A. & Metzger, H. Immun. Today 14, 222–226 (1993).
    Article CAS Google Scholar
  2. Kolanus, W., Romeo, C. & Seed, B. Cell 74, 171–183 (1993).
    Article CAS Google Scholar
  3. Takata, M. et al. EMBO J. 13, 1341–1349 (1994).
    Article CAS Google Scholar
  4. Berridge, M. J. Nature 361, 315–325 (1993).
    Article ADS CAS Google Scholar
  5. Jones, S. V. P., Choi, O. H. & Beaven, M. A. FEBS Lett. 289, 47–50 (1991).
    Article CAS Google Scholar
  6. Choi, O. H. et al. J. Immun. 151, 5586–5595 (1993).
    CAS PubMed Google Scholar
  7. Ghosh, T. K., Bian, J. & Gill, D. L. J. biol. Chem. 269, 22628–22635 (1994).
    CAS PubMed Google Scholar
  8. Mattie, M., Brooker, G. & Spiegel, S. J. biol. Chem. 269, 3181–3188 (1994).
    CAS PubMed Google Scholar
  9. Kindman, L. A., Kim, S., McDonald, T. V. & Gardner, P. J. biol. Chem. 269, 13088–13091 (1994).
    CAS PubMed Google Scholar
  10. Olivera, A. & Spiegel, S. Nature 365, 557–560 (1993).
    Article ADS CAS Google Scholar
  11. Stoffel, W., Heimann, G. & Hellenbroich, B. Hoppe-Seyler's Z. physiol. Chem. 354, 562–566 (1973).
    Article CAS Google Scholar
  12. Louie, D. D., Kisic, A. & Schroefer, G. J. Jr J. biol. Chem. 251, 4557–4564 (1976).
    CAS PubMed Google Scholar
  13. Buehrer, B. M. & Bell, R. M. Adv. Lipid Res. 26, 59–67 (1993).
    CAS PubMed Google Scholar
  14. Stoffel, W., Hellenbroich, B. & Heimann, G. Hoppe-Seyler's Z. physiol. Chem. 354, 1311–1316 (1973).
    Article CAS Google Scholar
  15. Buehrer, B. M. & Bell, R. M. J. biol. Chem. 267, 3154–3159 (1992).
    CAS PubMed Google Scholar
  16. Scharenberg, A. M., Lin, S., Cuenod, B., Yamamura, H. & Kinet, J. P. EMBO J. 14, 3385–3394 (1995).
    Article CAS Google Scholar
  17. Jouvin, M. H. et al. J. biol. Chem. 269, 5918–5925 (1994).
    CAS PubMed Google Scholar

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Author notes

  1. Jean-Pierre Kinet: Laboratory of Allergy and Immunology, Beth Israel Hospital, and Department of Pathology, Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA

Authors and Affiliations

  1. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, 20852, USA
    Oksoon Hong Choi, Jae-Heup Kim & Jean-Pierre Kinet

Authors

  1. Oksoon Hong Choi
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  2. Jae-Heup Kim
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  3. Jean-Pierre Kinet
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Hong Choi, O., Kim, JH. & Kinet, JP. Calcium mobilization via sphingosine kinase in signalling by the FcɛRI antigen receptor.Nature 380, 634–636 (1996). https://doi.org/10.1038/380634a0

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