Src kinases: a hub for NMDA receptor regulation (original) (raw)

• Stehelin, D., Varmus, H. E., Bishop, J. M. & Vogt, P. K. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260, 170–173 (1976).
  CAS PubMed Google Scholar
• Kuo, W. L., Chung, K. C. & Rosner, M. R. Differentiation of central nervous system neuronal cells by fibroblast-derived growth factor requires at least two signaling pathways: roles for Ras and Src. Mol. Cell. Biol. 17, 4633–4643 (1997).
  CAS PubMed PubMed Central Google Scholar
• Hoffman-Kim, D. et al. pp60(c-src) is a negative regulator of laminin-1-mediated neurite outgrowth in chick sensory neurons. Mol. Cell. Neurosci. 21, 81–93 (2002).
  CAS PubMed Google Scholar
• Wang, Y. T. & Salter, M. W. Regulation of NMDA receptors by tyrosine kinases and phosphatases. Nature 369, 233–235 (1994). This was the first report to show that tyrosine phosphorylation regulates the function of NMDARs. Intracellular application of recombinant Src was found to potentiate NMDAR currents, making the NMDAR the first ion channel in the CNS to be shown to be modulated by SFKs.
  CAS PubMed Google Scholar
• Fadool, D. A., Holmes, T. C., Berman, K., Dagan, D. & Levitan, I. B. Tyrosine phosphorylation modulates current amplitude and kinetics of a neuronal voltage-gated potassium channel. J. Neurophysiol. 78, 1563–1573 (1997).
  CAS PubMed Google Scholar
• Cataldi, M. et al. Protein-tyrosine kinases activate while protein-tyrosine phosphatases inhibit L-type calcium channel activity in pituitary GH3 cells. J. Biol. Chem. 271, 9441–9446 (1996).
  CAS PubMed Google Scholar
• Moss, S. J., Gorrie, G. H., Amato, A. & Smart, T. G. Modulation of GABAA receptors by tyrosine phosphorylation. Nature 377, 344–348 (1995).
  CAS PubMed Google Scholar
• Wan, Q. et al. Modulation of GABAA receptor function by tyrosine phosphorylation of beta subunits. J. Neurosci. 17, 5062–5069 (1997).
  CAS PubMed PubMed Central Google Scholar
• Wang, K. et al. Regulation of the neuronal nicotinic acetylcholine receptor by Src family tyrosine kinases. J. Biol. Chem. 279, 8779–8786 (2004).
  CAS PubMed Google Scholar
• Sadowski, I., Stone, J. C. & Pawson, T. A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps. Mol. Cell. Biol. 6, 4396–4408 (1986).
  CAS PubMed PubMed Central Google Scholar
• Moran, M. F. et al. Src homology region 2 domains direct protein-protein interactions in signal transduction. Proc. Natl Acad. Sci. USA 87, 8622–8626 (1990).
  CAS PubMed PubMed Central Google Scholar
• Ren, R., Mayer, B. J., Cicchetti, P. & Baltimore, D. Identification of a ten-amino acid proline-rich SH3 binding site. Science 259, 1157–1161 (1993).
  CAS PubMed Google Scholar
• Resh, M. D. Interaction of tyrosine kinase oncoproteins with cellular membranes. Biochim. Biophys. Acta 1155, 307–322 (1993).
  CAS PubMed Google Scholar
• Okada, M. & Nakagawa, H. A protein tyrosine kinase involved in regulation of pp60c-src function. J. Biol. Chem. 264, 20886–20893 (1989).
  CAS PubMed Google Scholar
• Klages, S. et al. Ctk: a protein-tyrosine kinase related to Csk that defines an enzyme family. Proc. Natl Acad. Sci. USA 91, 2597–2601 (1994).
  CAS PubMed PubMed Central Google Scholar
• Liu, X. et al. Regulation of c-Src tyrosine kinase activity by the Src SH2 domain. Oncogene 8, 1119–1126 (1993).
  CAS PubMed Google Scholar
• Xu, W., Harrison, S. C. & Eck, M. J. Three-dimensional structure of the tyrosine kinase c-Src. Nature 385, 595–602 (1997).
  CAS PubMed Google Scholar
• Cooper, J. A., Gould, K. L., Cartwright, C. A. & Hunter, T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science 231, 1431–1434 (1986).
  CAS PubMed Google Scholar
• Superti-Furga, G., Fumagalli, S., Koegl, M., Courtneidge, S. A. & Draetta, G. Csk inhibition of c-Src activity requires both the SH2 and SH3 domains of Src. EMBO J. 12, 2625–2634 (1993).
  CAS PubMed PubMed Central Google Scholar
• Zheng, X. M., Wang, Y. & Pallen, C. J. Cell transformation and activation of pp60c-src by overexpression of a protein tyrosine phosphatase. Nature 359, 336–339 (1992).
  CAS PubMed Google Scholar
• Fang, K. S., Sabe, H., Saito, H. & Hanafusa, H. Comparative study of three protein-tyrosine phosphatases. Chicken protein-tyrosine phosphatase lambda dephosphorylates c-Src tyrosine 527. J. Biol. Chem. 269, 20194–20200 (1994).
  CAS PubMed Google Scholar
• Bjorge, J. D., Pang, A. & Fujita, D. J. Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. J. Biol. Chem. 275, 41439–41446 (2000).
  CAS PubMed Google Scholar
• Somani, A. K., Bignon, J. S., Mills, G. B., Siminovitch, K. A. & Branch, D. R. Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase. J. Biol. Chem. 272, 21113–21119 (1997).
  CAS PubMed Google Scholar
• Peng, Z. Y. & Cartwright, C. A. Regulation of the Src tyrosine kinase and Syp tyrosine phosphatase by their cellular association. Oncogene 11, 1955–1962 (1995).
  CAS PubMed Google Scholar
• Hanke, J. H. et al. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. J. Biol. Chem. 271, 695–701 (1996).
  CAS PubMed Google Scholar
• Ma, Y. C., Huang, J., Ali, S., Lowry, W. & Huang, X. Y. Src tyrosine kinase is a novel direct effector of G proteins. Cell 102, 635–646 (2000).
  CAS PubMed Google Scholar
• Thornton, C., Yaka, R., Dinh, S. & Ron, D. H-Ras modulates NMDA receptor function via inhibition of Src tyrosine kinase activity. J. Biol. Chem. 278, 23823–23829 (2003).
  CAS PubMed Google Scholar
• Smart, J. E. et al. Characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue (pp60c-src). Proc. Natl Acad. Sci. USA 78, 6013–6017 (1981).
  CAS PubMed PubMed Central Google Scholar
• Xu, W., Doshi, A., Lei, M., Eck, M. J. & Harrison, S. C. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol. Cell 3, 629–638 (1999).
  CAS PubMed Google Scholar
• Gonfloni, S., Weijland, A., Kretzschmar, J. & Superti-Furga, G. Crosstalk between the catalytic and regulatory domains allows bidirectional regulation of Src. Nature Struct. Biol. 7, 281–286 (2000).
  CAS PubMed Google Scholar
• McBain, C. J. & Mayer, M. L. _N_-methyl-D-aspartic acid receptor structure and function. Physiol. Rev. 74, 723–760 (1994).
  CAS PubMed Google Scholar
• Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P. & Grant, S. G. Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nature Neurosci. 3, 661–669 (2000).
  CAS PubMed Google Scholar
• Wang, Y. T., Yu, X. M. & Salter, M. W. Ca2+-independent reduction of _N_-methyl-D-aspartate channel activity by protein tyrosine phosphatase. Proc. Natl Acad. Sci. USA 93, 1721–1725 (1996).
  CAS PubMed PubMed Central Google Scholar
• Kohr, G. & Seeburg, P. H. Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family. J. Physiol. (Lond.) 492, 445–452 (1996).
  Google Scholar
• Chen, C. & Leonard, J. P. Protein tyrosine kinase-mediated potentiation of currents from cloned NMDA receptors. J. Neurochem. 67, 194–200 (1996).
  CAS PubMed Google Scholar
• Roche, S., Koegl, M., Barone, M. V., Roussel, M. F. & Courtneidge, S. A. DNA synthesis induced by some but not all growth factors requires Src family protein tyrosine kinases. Mol. Cell. Biol. 15, 1102–1109 (1995).
  CAS PubMed PubMed Central Google Scholar
• Yu, X. M., Askalan, R., Keil, G. J. & Salter, M. W. NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275, 674–678 (1997). The authors show that endogenous Src upregulates the activity of NMDAR channels. They also find that the action of Src requires a sequence within the unique domain of Src (Src(40–58)) and that Src is a component of the NMDAR complex.
  CAS PubMed Google Scholar
• Lu, Y. M., Roder, J. C., Davidow, J. & Salter, M. W. Src activation in the induction of long-term potentiation in CA1 hippocampal neurons. Science 279, 1363–1367 (1998). This paper presents evidence that Src activation is necessary and sufficient for the induction of LTP in CA1 pyramidal neurons in hippocampal slices. LTP induction is prevented by blocking Src and occluded by directly activating Src. Src activity is increased in CA1 hippocampal slices after tetanic stimulation of Schaffer collateral inputs.
  CAS PubMed Google Scholar
• Lei, G. et al. Gain control of _N_-methyl-D-aspartate receptor activity by receptor-like protein tyrosine phosphatase α. EMBO J. 21, 2977–2989 (2002). This paper shows that PTPα, an activator of SFKs, is a component of the NMDAR complex and potentiates NMDAR currents in a SFK-dependent manner. LTP in CA1 pyramidal neurons in hippocampal slices is reduced by inhibiting endogenous PTPα.
  CAS PubMed PubMed Central Google Scholar
• Bhandari, V., Lim, K. L. & Pallen, C. J. Physical and functional interactions between receptor-like protein-tyrosine phosphatase α and p59fyn. J. Biol. Chem. 273, 8691–8698 (1998).
  CAS PubMed Google Scholar
• Harder, K. W., Moller, N. P., Peacock, J. W. & Jirik, F. R. Protein-tyrosine phosphatase α regulates Src family kinases and alters cell-substratum adhesion. J. Biol. Chem. 273, 31890–31900 (1998).
  CAS PubMed Google Scholar
• Ponniah, S., Wang, D. Z., Lim, K. L. & Pallen, C. J. Targeted disruption of the tyrosine phosphatase PTPα leads to constitutive downregulation of the kinases Src and Fyn. Curr. Biol. 9, 535–538 (1999).
  CAS PubMed Google Scholar
• Huang, Y. et al. CAKβ/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus. Neuron 29, 485–496 (2001).
  CAS PubMed Google Scholar
• Suzuki, T. & Okumura-Noji, K. NMDA receptor subunits ε1 (NR2A) and ε2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain. Biochem. Biophys. Res. Commun. 216, 582–588 (1995).
  CAS PubMed Google Scholar
• Kalia, L. V. & Salter, M. W. Interactions between Src family protein tyrosine kinases and PSD-95. Neuropharmacology 45, 720–728 (2003).
  CAS PubMed Google Scholar
• Yaka, R. et al. NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1. Proc. Natl Acad. Sci. USA 99, 5710–5715 (2002).
  CAS PubMed PubMed Central Google Scholar
• Roche, S., Fumagalli, S. & Courtneidge, S. A. Requirement for Src family protein tyrosine kinases in G2 for fibroblast cell division. Science 269, 1567–1569 (1995).
  CAS PubMed Google Scholar
• Ali, D. W. & Salter, M. W. NMDA receptor regulation by Src kinase signalling in excitatory synaptic transmission and plasticity. Curr. Opin. Neurobiol. 11, 336–342 (2001).
  CAS PubMed Google Scholar
• Oyama, T. et al. Immunocytochemical localization of the striatal enriched protein tyrosine phosphatase in the rat striatum: a light and electron microscopic study with a complementary DNA-generated polyclonal antibody. Neuroscience 69, 869–880 (1995).
  CAS PubMed Google Scholar
• Boulanger, L. M. et al. Cellular and molecular characterization of a brain-enriched protein tyrosine phosphatase. J. Neurosci. 15, 1532–1544 (1995).
  CAS PubMed PubMed Central Google Scholar
• Pelkey, K. A. et al. Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation. Neuron 34, 127–138 (2002). The authors show that STEP is a component of the NMDAR complex. STEP was the first PTP to be found to suppress the activity of NMDARs by opposing the action of Src. The authors also show that activity of STEP tonically suppresses induction of LTP in CA1 neurons; inhibiting STEP produces LTP even without tetanus.
  CAS PubMed Google Scholar
• Hironaka, K., Umemori, H., Tezuka, T., Mishina, M. & Yamamoto, T. The protein-tyrosine phosphatase PTPMEG interacts with glutamate receptor δ2 and ε subunits. J. Biol. Chem. 275, 16167–16173 (2000).
  CAS PubMed Google Scholar
• Lin, S. Y. et al. Brain-derived neurotrophic factor enhances association of protein tyrosine phosphatase PTP1D with the NMDA receptor subunit NR2B in the cortical postsynaptic density. Brain Res. Mol. Brain Res. 70, 18–25 (1999).
  CAS PubMed Google Scholar
• Levine, E. S., Dreyfus, C. F., Black, I. B. & Plummer, M. R. Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors. Proc. Natl Acad. Sci. USA 92, 8074–8077 (1995).
  CAS PubMed PubMed Central Google Scholar
• Lin, S. Y. et al. BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities. Brain Res. Mol. Brain Res. 55, 20–27 (1998).
  CAS PubMed Google Scholar
• Moon, I. S., Apperson, M. L. & Kennedy, M. B. The major tyrosine-phosphorylated protein in the postsynaptic density fraction is _N_-methyl-D-aspartate receptor subunit 2B. Proc. Natl Acad. Sci. USA 91, 3954–3958 (1994). This paper is the first to report tyrosine phosphorylation of an NR2 subunit, namely NR2B. The results indicate that NMDAR function might be regulated by tyrosine phosphorylation of a receptor subunit protein and/or that NMDARs participate in signalling through tyrosine phosphorylation.
  CAS PubMed PubMed Central Google Scholar
• Lau, L. F. & Huganir, R. L. Differential tyrosine phosphorylation of _N_-methyl-D-aspartate receptor subunits. J. Biol. Chem. 270, 20036–20041 (1995).
  CAS PubMed Google Scholar
• Yang, M. & Leonard, J. P. Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites phosphorylated by coexpression with v-Src. J. Neurochem. 77, 580–588 (2001).
  CAS PubMed Google Scholar
• Nakazawa, T. et al. Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR ε2 (NR2B) subunit of the _N_-methyl-D-aspartate receptor. J. Biol. Chem. 276, 693–699 (2001). References 58 and 59 identify tyrosine residues that are phosphorylated by SFKs in the C-terminal tails of NR2A and NR2B, respectively. The main site of phosphorylation of NR2B is Y1472. With a phosphospecific antibody, this residue is found to be basally phosphorylated in the brain and to be hyperphosphorylated in CA1 hippocampal slices after tetanic stimulation of Schaffer collateral inputs.
  CAS PubMed Google Scholar
• Cheung, H. H. & Gurd, J. W. Tyrosine phosphorylation of the _N_-methyl-D-aspartate receptor by exogenous and postsynaptic density-associated Src-family kinases. J. Neurochem. 78, 524–534 (2001).
  CAS PubMed Google Scholar
• Zheng, F., Gingrich, M. B., Traynelis, S. F. & Conn, P. J. Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition. Nature Neurosci. 1, 185–191 (1998). The authors show that for NR1/NR2A and NR1/NR2B receptors expressed heterologously, tyrosine phosphorylation potentiates NMDAR currents by reducing tonic inhibition by zinc. So, an intracellular biochemical event, phosphorylation, affects regulation at an extracellular site on the NMDAR.
  CAS PubMed Google Scholar
• Xiong, Z. G. et al. Src potentiation of NMDA receptors in hippocampal and spinal neurons is not mediated by reducing zinc inhibition. J. Neurosci. 19, RC37 (1999). This paper shows that the mechanism identified in reference 61 is not responsible for the upregulation of NMDAR activity by Src in hippocampal or spinal cord neurons.
  CAS PubMed PubMed Central Google Scholar
• Nada, S. et al. Identification of PSD-93 as a substrate for the Src family tyrosine kinase Fyn. J. Biol. Chem. 278, 47610–47621 (2003).
  CAS PubMed Google Scholar
• Gurd, J. W. & Bissoon, N. The _N_-methyl-D-aspartate receptor subunits NR2A and NR2B bind to the SH2 domains of phospholipase C-γ. J. Neurochem. 69, 623–630 (1997).
  CAS PubMed Google Scholar
• Hisatsune, C., Umemori, H., Mishina, M. & Yamamoto, T. Phosphorylation-dependent interaction of the _N_-methyl-D-aspartate receptor epsilon 2 subunit with phosphatidylinositol 3-kinase. Genes Cells 4, 657–666 (1999).
  CAS PubMed Google Scholar
• Takagi, N. et al. The effect of transient global ischemia on the interaction of Src and Fyn with the _N_-methyl-D-aspartate receptor and postsynaptic densities: possible involvement of Src homology 2 domains. J. Cereb. Blood Flow Metab. 19, 880–888 (1999).
  CAS PubMed Google Scholar
• Bi, R., Rong, Y., Bernard, A., Khrestchatisky, M. & Baudry, M. Src-mediated tyrosine phosphorylation of NR2 subunits of _N_-methyl-D-aspartate receptors protects from calpain-mediated truncation of their C-terminal domains. J. Biol. Chem. 275, 26477–26483 (2000).
  CAS PubMed Google Scholar
• Rong, Y., Lu, X., Bernard, A., Khrestchatisky, M. & Baudry, M. Tyrosine phosphorylation of ionotropic glutamate receptors by Fyn or Src differentially modulates their susceptibility to calpain and enhances their binding to spectrin and PSD-95. J. Neurochem. 79, 382–390 (2001).
  CAS PubMed Google Scholar
• Malenka, R. C. & Nicoll, R. A. Long-term potentiation — a decade of progress? Science 285, 1870–1874 (1999).
  CAS PubMed Google Scholar
• Grosshans, D. R., Clayton, D. A., Coultrap, S. J. & Browning, M. D. LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1. Nature Neurosci. 5, 27–33 (2002). The authors show that LTP in the CA1 region of the adult rat hippocampus leads to rapid surface expression of NMDARs. NMDARs were previously thought to undergo only relatively slow turnover. PKC and SFK activities were required, because inhibition of either PKC or SFKs prevented the increase in NMDAR surface expression.
  CAS PubMed Google Scholar
• Vissel, B., Krupp, J. J., Heinemann, S. F. & Westbrook, G. L. A use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux. Nature Neurosci. 4, 587–596 (2001). Recombinant NR1/NR2A receptors expressed in HEK293 cells exhibit a steady decline of the peak amplitudes of NMDAR currents with regular agonist application. This activity-dependent decline of NMDAR-mediated currents is prevented by intracellular application of recombinant Src or a PTP inhibitor, and involves Y842 in the NR2A C-terminal tail.
  CAS PubMed Google Scholar
• Roche, K. W. et al. Molecular determinants of NMDA receptor internalization. Nature Neurosci. 4, 794–802 (2001).
  CAS PubMed Google Scholar
• Marsh, M. & McMahon, H. T. The structural era of endocytosis. Science 285, 215–220 (1999).
  CAS PubMed Google Scholar
• Marino, M. J., Rouse, S. T., Levey, A. I., Potter, L. T. & Conn, P. J. Activation of the genetically defined m1 muscarinic receptor potentiates _N_-methyl-D-aspartate (NMDA) receptor currents in hippocampal pyramidal cells. Proc. Natl Acad. Sci. USA 95, 11465–11470 (1998).
  CAS PubMed PubMed Central Google Scholar
• Lu, W. Y. et al. G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors. Nature Neurosci. 2, 331–338 (1999). This paper is the first description of a signalling pathway upstream of the SFK-mediated upregulation of NMDARs. Stimulation of endogenous PKC potentiates NMDAR currents and the PKC-stimulated potentiation requires Src. Activating either muscarinic or lysophosphatidic acid types of GPCRs upregulates NMDAR currents through the PKC–Src cascade.
  CAS PubMed Google Scholar
• Xiong, Z. G. et al. Regulation of _N_-methyl-D-aspartate receptor function by constitutively active protein kinase C. Mol. Pharmacol. 54, 1055–1063 (1998).
  CAS PubMed Google Scholar
• Dikic, I., Tokiwa, G., Lev, S., Courtneidge, S. A. & Schlessinger, J. A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation. Nature 383, 547–550 (1996).
  CAS PubMed Google Scholar
• Kotecha, S. A. et al. Co-stimulation of mGluR5 and NMDA receptors is required for potentiation of excitatory synaptic transmission in hippocampal neurons. J. Biol. Chem. 278, 27742–27749 (2003).
  CAS PubMed Google Scholar
• Benquet, P., Gee, C. E. & Gerber, U. Two distinct signaling pathways upregulate NMDA receptor responses via two distinct metabotropic glutamate receptor subtypes. J. Neurosci. 22, 9679–9686 (2002).
  CAS PubMed PubMed Central Google Scholar
• Heidinger, V. et al. Metabotropic glutamate receptor 1-induced upregulation of NMDA receptor current: mediation through the Pyk2/Src-family kinase pathway in cortical neurons. J. Neurosci. 22, 5452–5461 (2002).
  CAS PubMed PubMed Central Google Scholar
• Chang, B. Y., Conroy, K. B., Machleder, E. M. & Cartwright, C. A. RACK1, a receptor for activated C kinase and a homolog of the β subunit of G proteins, inhibits activity of src tyrosine kinases and growth of NIH 3T3 cells. Mol. Cell. Biol. 18, 3245–3256 (1998).
  CAS PubMed PubMed Central Google Scholar
• Roberto, M. & Brunelli, M. PACAP-38 enhances excitatory synaptic transmission in the rat hippocampal CA1 region. Learn. Mem. 7, 303–311 (2000).
  CAS PubMed PubMed Central Google Scholar
• Yaka, R., He, D. Y., Phamluong, K. & Ron, D. Pituitary adenylate cyclase-activating polypeptide (PACAP(1-38)) enhances _N_-methyl-D-aspartate receptor function and brain-derived neurotrophic factor expression via RACK1. J. Biol. Chem. 278, 9630–9638 (2003).
  CAS PubMed Google Scholar
• Vaudry, D. et al. Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol. Rev. 52, 269–324 (2000).
  CAS PubMed Google Scholar
• Takasu, M. A., Dalva, M. B., Zigmond, R. E. & Greenberg, M. E. Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors. Science 295, 491–495 (2002). This is the first report of a receptor protein tyrosine kinase pathway upstream of NMDAR potentiation by SFKs. Activation of EphB receptors results in increased NMDAR-dependent Ca 2+ responses and tyrosine phosphorylation of NR2B subunits. SFK activation is necessary for the EphB-mediated NR2B phosphorylation.
  CAS PubMed Google Scholar
• Dalva, M. B. et al. EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell 103, 945–956 (2000).
  CAS PubMed Google Scholar
• Manabe, T. et al. Regulation of long-term potentiation by H-Ras through NMDA receptor phosphorylation. J. Neurosci. 20, 2504–2511 (2000).
  CAS PubMed PubMed Central Google Scholar
• Finkbeiner, S. & Greenberg, M. E. Ca2+-dependent routes to Ras: mechanisms for neuronal survival, differentiation, and plasticity? Neuron 16, 233–236 (1996).
  CAS PubMed Google Scholar
• Viviani, B. et al. Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J. Neurosci. 23, 8692–8700 (2003). Activation of IL-1RI enhances NMDAR-mediated Ca 2+ responses in cultured hippocampal neurons and this is prevented by SFK inhibition. SFKs do not directly facilitate IL-1RI-mediated signal transduction and thus the IL-1RI pathway is upstream of SFK activity.
  CAS PubMed PubMed Central Google Scholar
• Hakansson, M. L., Brown, H., Ghilardi, N., Skoda, R. C. & Meister, B. Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J. Neurosci. 18, 559–572 (1998).
  CAS PubMed PubMed Central Google Scholar
• Shanley, L. J., Irving, A. J. & Harvey, J. Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity. J. Neurosci. 21, RC186 (2001).
  CAS PubMed PubMed Central Google Scholar
• Lin, B., Arai, A. C., Lynch, G. & Gall, C. M. Integrins regulate NMDA receptor-mediated synaptic currents. J. Neurophysiol. 89, 2874–2878 (2003).
  CAS PubMed Google Scholar
• Giancotti, F. G. & Ruoslahti, E. Integrin signaling. Science 285, 1028–1032 (1999).
  CAS PubMed Google Scholar
• Grant, S. G. et al. Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. Science 258, 1903–1910 (1992).
  CAS PubMed Google Scholar
• O'Dell, T. J., Kandel, E. R. & Grant, S. G. Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors. Nature 353, 558–560 (1991). This paper reports the first evidence that tyrosine kinases are necessary for the induction, but not the maintenance, of LTP in area CA1 of the hippocampus.
  CAS PubMed Google Scholar
• Rosenblum, K., Dudai, Y. & Richter-Levin, G. Long-term potentiation increases tyrosine phosphorylation of the _N_-methyl-D-aspartate receptor subunit 2B in rat dentate gyrus in vivo. Proc. Natl Acad. Sci. USA 93, 10457–10460 (1996).
  CAS PubMed PubMed Central Google Scholar
• Rostas, J. A. et al. Enhanced tyrosine phosphorylation of the 2B subunit of the _N_-methyl-D-aspartate receptor in long-term potentiation. Proc. Natl Acad. Sci. USA 93, 10452–10456 (1996).
  CAS PubMed PubMed Central Google Scholar
• Petrone, A. et al. Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation. EMBO J. 22, 4121–4131 (2003).
  CAS PubMed PubMed Central Google Scholar
• Lauri, S. E., Taira, T. & Rauvala, H. High-frequency synaptic stimulation induces association of fyn and c-src to distinct phosphorylated components. Neuroreport 11, 997–1000 (2000).
  CAS PubMed Google Scholar
• Yu, X. M. & Salter, M. W. Gain control of NMDA-receptor currents by intracellular sodium. Nature 396, 469–474 (1998).
  CAS PubMed Google Scholar
• Salter, M. W. Src, _N_-methyl-D-aspartate (NMDA) receptors, and synaptic plasticity. Biochem. Pharmacol. 56, 789–798 (1998).
  CAS PubMed Google Scholar
• Yu, X. M. & Salter, M. W. Src, a molecular switch governing gain control of synaptic transmission mediated by _N_-methyl-D-aspartate receptors. Proc. Natl Acad. Sci. USA 96, 7697–7704 (1999).
  CAS PubMed PubMed Central Google Scholar
• Woolf, C. J. & Salter, M. W. Neuronal plasticity: increasing the gain in pain. Science 288, 1765–1769 (2000).
  CAS PubMed Google Scholar
• Guo, W. et al. Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord during the development and maintenance of inflammatory hyperalgesia. J. Neurosci. 22, 6208–6217 (2002).
  CAS PubMed PubMed Central Google Scholar
• Battaglia, A. A., Sehayek, K., Grist, J., McMahon, S. B. & Gavazzi, I. EphB receptors and ephrin-B ligands regulate spinal sensory connectivity and modulate pain processing. Nature Neurosci. 6, 339–340 (2003).
  CAS PubMed Google Scholar
• Mody, I. Synaptic plasticity in kindling. Adv. Neurol. 79, 631–643 (1999).
  CAS PubMed Google Scholar
• Cain, D. P., Grant, S. G., Saucier, D., Hargreaves, E. L. & Kandel, E. R. Fyn tyrosine kinase is required for normal amygdala kindling. Epilepsy Res. 22, 107–114 (1995).
  CAS PubMed Google Scholar
• Kojima, N., Ishibashi, H., Obata, K. & Kandel, E. R. Higher seizure susceptibility and enhanced tyrosine phosphorylation of _N_-methyl-D-aspartate receptor subunit 2B in fyn transgenic mice. Learn. Mem. 5, 429–445 (1998).
  CAS PubMed PubMed Central Google Scholar
• Moussa, R. C., Ikeda-Douglas, C. J., Thakur, V., Milgram, N. W. & Gurd, J. W. Seizure activity results in increased tyrosine phosphorylation of the _N_-methyl-D-aspartate receptor in the hippocampus. Brain Res. Mol. Brain Res. 95, 36–47 (2001).
  CAS PubMed Google Scholar
• Sanna, P. P. et al. A role for Src kinase in spontaneous epileptiform activity in the CA3 region of the hippocampus. Proc. Natl Acad. Sci. USA 97, 8653–8657 (2000). This paper shows that Src kinase activity is increased in an in vitro model of epileptiform activity in the CA3 region of hippocampal slices. The frequency of epileptiform discharges is reduced by inhibition of SFKs, consistent with a role for SFKs in epilepsy.
  CAS PubMed PubMed Central Google Scholar
• Takagi, N. et al. Transient ischemia differentially increases tyrosine phosphorylation of NMDA receptor subunits 2A and 2B. J. Neurochem. 69, 1060–1065 (1997).
  CAS PubMed Google Scholar
• Cheung, H. H. et al. Altered association of protein tyrosine kinases with postsynaptic densities after transient cerebral ischemia in the rat brain. J. Cereb. Blood Flow Metab. 20, 505–512 (2000).
  CAS PubMed Google Scholar
• Cheung, H. H., Teves, L., Wallace, M. C. & Gurd, J. W. Inhibition of protein kinase C reduces ischemia-induced tyrosine phosphorylation of the _N_-methyl-D-aspartate receptor. J. Neurochem. 86, 1441–1449 (2003).
  CAS PubMed Google Scholar
• Hashimoto, R., Fujimaki, K., Jeong, M. R., Christ, L. & Chuang, D. M. Lithium-induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: a role in neuroprotection against _N_-methyl-D-aspartate receptor-mediated excitotoxicity. FEBS Lett. 538, 145–148 (2003).
  CAS PubMed Google Scholar
• Cattaneo, E. et al. Loss of normal huntingtin function: new developments in Huntington's disease research. Trends Neurosci. 24, 182–188 (2001).
  CAS PubMed Google Scholar
• Song, C., Zhang, Y., Parsons, C. G. & Liu, Y. F. Expression of polyglutamine-expanded huntingtin induces tyrosine phosphorylation of _N_-methyl-D-aspartate receptors. J. Biol. Chem. 278, 33364–33369 (2003).
  CAS PubMed Google Scholar
• Sun, Y., Savanenin, A., Reddy, P. H. & Liu, Y. F. Polyglutamine-expanded huntingtin promotes sensitization of _N_-methyl-D-aspartate receptors via post–synaptic density 95. J. Biol. Chem. 276, 24713–24718 (2001).
  CAS PubMed Google Scholar