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Calcium mobilization via sphingosine kinase in signalling by the FcɛRI antigen receptor

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,Ki, 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 

Download references

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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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