Letter | Published:

Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors

Nature volume 383, pages 8992 (05 September 1996) | Download Citation

Subjects

Abstract

STIMULATION of two metabotropic glutamate-receptor subtypes, mGluRl and mGluRS, triggers the release of Ca2+ from intra-cellular stores through the inositol-(1,4,5) trisphosphate (InsP3) pathway1,3. Here we report that glutamate induces single-peaked intracellular Ca2+ mobilization in mGluR1α-transfected cells but elicits Ca2+ oscillations in mGluRSa-transfected cells. The response patterns of the intracellular Ca2+ increase depend upon the identity of a single amino acid, aspartate (at position 854) or threonine (at position 840), located within the G-protein-inter-acting domains of mGluR1α and mGluR5a, respectively. Pharmacological and peptide mapping analyses indicated that phosphorylation of the threonine residue at position 840 of mGluRSa by protein kinase C (PKC) is responsible for the generation of Ca2+ oscillations in mGluR5a-expressing cells. To our knowledge this is the first evidence that PKC phosphorylation of G-protein-coupled receptors is important in producing oscillations in intracellular Ca2+ signalling.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , , , & Nature 349, 760–765 (1991).

  2. 2.

    et al. J. Biol. Chem. 267, 13361–13368 (1992).

  3. 3.

    & Neuron 8, 757–765 (1992).

  4. 4.

    et al. Proc. Natl Acad. Sci. USA 87, 2466–2470 (1990).

  5. 5.

    , , & EMBO J. 13, 342–348 (1994).

  6. 6.

    & J. Biol. Chem. 266, 15555–15558 (1991).

  7. 7.

    , , , & Proc. Natl Acad. Sci. USA 86, 7017–7021 (1989).

  8. 8.

    et al. Biochem. Biophys. Res. Commun. 135, 397–402 (1986).

  9. 9.

    et al. J. Biol. Chem. 265, 4315–4320 (1990).

  10. 10.

    et al. J. Biol. Chem. 257, 7847–7851 (1982).

  11. 11.

    , , , & Cancer Res. 48, 3168–3172 (1988).

  12. 12.

    , & J. Biol. Chem. 262, 772–777 (1987).

  13. 13.

    & Cell 69, 283–294 (1992).

  14. 14.

    et al. Science 257, 251–255 (1992).

  15. 15.

    Nature 361, 315–325 (1993).

  16. 16.

    Cell 80, 259–268 (1995).

  17. 17.

    , , & Science 251, 75–78 (1991).

  18. 18.

    , , & J. Biol. Chem. 268, 8425–8428 (1993).

  19. 19.

    , & EMBO J. 8, 3711–3718 (1989).

  20. 20.

    J. Physiol. (Lond.) 406, 35–53 (1988).

  21. 21.

    & Nature 316, 541–542 (1985).

  22. 22.

    , & J. Neurosci. 15, 6103–6109 (1995).

  23. 23.

    , , & Science 247, 470–473 (1990).

  24. 24.

    & Nucleic Acids Res. 18, 5322 (1990).

  25. 25.

    , & J. Biol. Chem. 260, 3440–3450 (1985).

  26. 26.

    , & J. Biol. Chem. 265, 3577–3584 (1990).

  27. 27.

    , & FEBS Lett. 367, 301–305 (1995).

  28. 28.

    et al. Neurosci. Lett. 163, 53–57 (1993).

  29. 29.

    , & Biochemistry 34, 9488–9499 (1995).

Download references

Author information

Affiliations

  1. Neuroscience & Gastrointestinal Research Laboratory, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305, Japan

    • Shigeki Kawabata
    • , Rie Tsutsumi
    • , Atsuyuki Kohara
    • , Tokio Yamaguchi
    •  & Masamichi Okada
  2. Department of Biological Sciences, Kyoto University Faculty of Medicine, Kyoto 606, Japan

    • Shigetada Nakanishi

Authors

  1. Search for Shigeki Kawabata in:

  2. Search for Rie Tsutsumi in:

  3. Search for Atsuyuki Kohara in:

  4. Search for Tokio Yamaguchi in:

  5. Search for Shigetada Nakanishi in:

  6. Search for Masamichi Okada in:

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/383089a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.