Protein tyrosine kinase-mediated potentiation of currents from cloned NMDA receptors.
Although serine/threonine phosphorylation has been more commonly recognized as a mechanism to modulate the function of ion channels and receptors, tyrosine phosphorylation is under increasing scrutiny. An important subtype of glutamate receptor, the NMDA receptor, is shown to be regulated by insulin via protein tyrosine kinase (PTK). NMDA currents through cloned receptors are potentiated by insulin in a subunit-specific manner. The insulin-mediated potentiation of NMDA current is diminished by inhibitors of PTKs. At least one exogenous cytosolic PTK, pp60c-src, is also able to potentiate NMDA current. Because later application of PTK inhibitors can reverse the seemingly stable insulin-mediated potentiation of NMDA current, it appears that tyrosine residues responsible for potentiation are continually rephosphorylated by some long-term PTK activity that was induced via insulin treatment.
Chen
C
C
Department of Biological Sciences, Laboratory for Molecular Biology, University of Illinois at Chicago, 60607-7060, USA.
Leonard
J P
JP
D000818:Animals; D003001:Cloning, Molecular; D004357:Drug Synergism; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D007328:Insulin / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes / Q000737:chemistry / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000494:pharmacology; D011972:Receptor, Insulin / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000235:genetics*; D014982:Xenopus laevis
D018690:Excitatory Amino Acid Agonists; D007328:Insulin; D016194:Receptors, N-Methyl-D-Aspartate; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D016392:Proto-Oncogene Proteins pp60(c-src)