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Regulation of NMDA receptors by tyrosine kinases and phosphatases


PROTEIN-TYROSINE kinases (PTKs) and protein-tyrosine phosphatases (PTPs) are key enzymes in signal-transduction pathways for a wide range of cellular processes1,2. PTKs and PTPs are highly expressed in the central nervous system3, which is consistent with the importance of tyrosine phosphorylation in neuronal function4–6. Protein phosphorylation is known to be involved in the regulation of neurotransmitter receptors7,8, but the effects of tyrosine phosphorylation on neurotransmitter receptor function in the central nervous system are unknown. Here we present evidence that in mammalian central neurons tyrosine phosphorylation regulates the function of the NMDA (N-methyl-D-aspartate) receptor, a subtype of excitatory amino-acid receptor9,10. NMDA-receptor-mediated whole-cell currents and intracellular Ca2+ responses are depressed by inhibition of PTKs. Conversely, NMDA currents are potentiated by intracellular application of the well characterized PTK pp60c-src. NMDA currents are also potentiated by intracellular administration of an inhibitor of PTPs. Protein-tyrosine phosphorylation is a new mechanism for regulating NMDA receptors and may be important in neuronal development, plasticity and toxicity.

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  1. Hunter, T. & Cooper, J. A. A. Rev. Biochem. 54, 897–930 (1985).

    CAS  Article  Google Scholar 

  2. Fischer, E. H., Charbonneau, H. & Tonks, N. K. Science 253, 401–406 (1991).

    CAS  Article  ADS  Google Scholar 

  3. Wager, K. R., Mei, L. & Huganir, R. L. Curr. Opin. Neurobiol. 1, 65–73 (1991).

    Article  Google Scholar 

  4. Catarsi, S. & Drapeau, P. Nature 363, 353–355 (1993).

    CAS  Article  ADS  Google Scholar 

  5. O'Dell, T. J., Kandel, E. R. & Grant, S. G. Nature 353, 558–560 (1991).

    CAS  Article  ADS  Google Scholar 

  6. Grant, S. G. N. et al. Science 258, 1903–1910 (1992).

    CAS  Article  ADS  Google Scholar 

  7. Walaas, S. I. & Greengard, P. Pharmac. Rev. 43, 299–349 (1991).

    CAS  Google Scholar 

  8. Raymond, L. A., Blackstone, C. D. & Huganir, R. L. Trends Neurosci. 16, 147–153 (1993).

    CAS  Article  Google Scholar 

  9. Mayer, M. L. & Westbrook, G. L. Prog. Neurobiol. 28, 197–276 (1987).

    CAS  Article  Google Scholar 

  10. Gasic, G. P. & Hollmann, M. A. Rev. Physiol. 54, 507–536 (1992).

    CAS  Article  Google Scholar 

  11. Mayer, M. L. & Westbrook, G. L. J. Physiol., Lond. 354, 29–53 (1984).

    CAS  Article  Google Scholar 

  12. Akiyama, T. et al. J. biol. Chem. 262, 5592–5595 (1987).

    CAS  PubMed  Google Scholar 

  13. Onoda, T. et al. J. nat. Prod. 52, 1252–1257 (1989).

    CAS  Article  Google Scholar 

  14. Brickell, P. M. Crit. Rev. Oncogen. 3, 401–446 (1992).

    CAS  Google Scholar 

  15. Swarup, G., Cohen, S. & Garbers, D. L. Biochem. biophys. Res. Commun. 107, 1104–1109 (1982).

    CAS  Article  Google Scholar 

  16. Schlessinger, J. & Ullrich, A. Neuron 9, 383–391 (1992).

    CAS  Article  Google Scholar 

  17. Chiba, T. et al. Nature 362, 646–648 (1993).

    CAS  Article  ADS  Google Scholar 

  18. Pan, M. G., Florio, T. & Stork, P. J. S. Science 256, 1215–1217 (1992).

    CAS  Article  ADS  Google Scholar 

  19. Bading, H. & Greenberg, M. E. Science 253, 912–914 (1991).

    CAS  Article  ADS  Google Scholar 

  20. Zachary, I., Gil, J., Lehmann, W., Sinnet-Smith, J. & Rozengurt, E. Proc. natn. Acad. Sci. U.S.A. 88, 4577–4581 (1991).

    CAS  Article  ADS  Google Scholar 

  21. Horn, R. & Marty, A. J. gen. Physiol. 92, 145–159 (1988).

    CAS  Article  Google Scholar 

  22. Salter, M. W. & Hicks, J. L. J. Neurosci. 14, 1563–1575 (1994).

    CAS  Article  Google Scholar 

  23. Johnson, J. W. & Ascher, P. Nature 325, 529–531 (1987).

    CAS  Article  ADS  Google Scholar 

  24. Wang, L. Y., Salter, M. W. & MacDonald, J. F. Science 253, 1132–1135 (1991).

    CAS  Article  ADS  Google Scholar 

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Wang, Y., Salter, M. Regulation of NMDA receptors by tyrosine kinases and phosphatases. Nature 369, 233–235 (1994).

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