PMID: 11902114Mar 21, 2002Paper

Phosphatidylinositol 3-kinase is a central mediator of NMDA receptor signalling to MAP kinase (Erk1/2), Akt/PKB and CREB in striatal neurones

Journal of Neurochemistry
Michael S PerkintonRobert J Williams

Abstract

Ca2+ influx through NMDA receptors can initiate molecular changes in neurones which may underlie synaptic plasticity, neuronal development, survival and excitotoxicity. Signalling through the MAP kinase (Erk1/2) cascade may be central to these processes. We previously demonstrated that Ca2+-permeable AMPA receptors activate Erkl/2 through a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent mechanism. We now report that NMDA receptor activation of Erk1/2 was also blocked by inhibitors of PI 3-kinase (LY 294002, wortmannin). In addition, pre-treatment of neurones with pertussis toxin inhibited NMDA-induced Erk1/2 activation, indicating a role for heterotrimeric Gi/o proteins. PI 3-kinase directs activation of the serine-threonine kinase Akt (PKB). Treatment of striatal neurones with glutamate induced a rapid Ca2+-dependent and PI 3-kinase-dependent phosphorylation of Akt (Ser473), which was not blocked by the Mek inhibitors PD98059 or U0126. Targets for Erk1/2 and Akt pathways include transcription factors. Glutamate-induced phosphorylation of cAMP response element binding protein (CREB; Ser133) was partially blocked with either PD98059, U0126, LY294002 or wortmannin but was very strongly inhibited on co-application of LY2940...Continue Reading

Citations

May 12, 2005·Der Nervenarzt·G SchumannJ Treutlein
Dec 31, 2010·Neurotoxicity Research·Valentina L Savchenko, John D Boughter
May 10, 2003·Neurobiology of Learning and Memory·Yolanda RoblesSandra Peña de Ortiz
Sep 3, 2002·Nature Medicine·Jeffrey D Rothstein
Oct 31, 2002·The European Journal of Neuroscience·Barbara MontiAntonio Contestabile
Apr 11, 2013·PloS One·Elizabeth A CoreyBarry W Ache
Apr 18, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sophie PezetStephen B McMahon
Feb 16, 2005·Developmental Neuroscience·Kelvin C Luk, Abbas F Sadikot
Nov 29, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yubin WangMichel Baudry
Sep 30, 2004·Science's STKE : Signal Transduction Knowledge Environment·Ru-Rong Ji, Gary Strichartz
Sep 17, 2004·Journal of Neuroscience Research·Alejandro MillánArturo Ortega
Feb 16, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Richard Hampl, Marie Bicíková
Feb 13, 2007·Neurobiology of Aging·Jonathan J AbbottRobert J Williams
Nov 19, 2004·The European Journal of Neuroscience·Sriram M Ajay, Upinder S Bhalla
May 5, 2005·The European Journal of Neuroscience·Sophie PezetStephen B McMahon
Mar 25, 2005·The European Journal of Neuroscience·Xavier XifroJosé Rodríguez-Alvarez
Mar 16, 2004·The European Journal of Neuroscience·Limin MaoJohn Q Wang
Dec 20, 2003·Annals of the New York Academy of Sciences·Ian A Paul, Phil Skolnick
Aug 19, 2007·Journal of Neurochemistry·Nobutaka OhkuboNoriaki Mitsuda
Feb 19, 2005·Neurobiology of Aging·Liou Y SunAndrzej Bartke

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