Increased tyrosine phosphorylation of PSD-95 by Src family kinases after brain ischaemia

The Biochemical Journal
Cai-Ping DuXiao-Yu Hou

Abstract

PSD (postsynaptic density)-95, a scaffold protein that tethers NMDA (N-methyl-D-aspartate) receptors to signal molecules, is implicated in pathological events resulting from excitotoxicity. The present study demonstrates that brain ischaemia and reperfusion increase the tyrosine phosphorylation of PSD-95 in the rat hippocampus. PP2, a specific inhibitor of SrcPTKs (Src family protein tyrosine kinases), prevents the ischaemia-induced increases not only in the tyrosine phosphorylation of PSD-95, but also in the interaction between PSD-95 and Src kinases. PSD-95 is phosphorylated either by purified Src/Fyn kinases in vitro or by co-expression of constitutively active Src/Fyn in COS7 cells. The results suggest that SrcPTKs are involved in PSD-95 phosphorylation. The single Tyr(523) mutation to phenylalanine (Y523F) reduces the Src/Fyn-mediated phosphorylation of PSD-95 in COS7 cells and in vitro. As shown with a rabbit polyclonal antibody against phospho-PSD-95 (Tyr(523)), Tyr(523) phosphorylation is responsible for the increased tyrosine phosphorylation of PSD-95 induced by ischaemia in the rat hippocampus. In cultured hippocampal neurons, overexpression of PSD-95 Y523F, but not PSD-95 Y533F, abolishes the facilitating effect of P...Continue Reading

References

Jun 1, 1997·Trends in Neurosciences·M B Kennedy
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·T TezukaT Yamamoto
Jun 12, 2001·Current Opinion in Neurobiology·S Cull-CandyM Farrant
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·M Sheng
Feb 8, 2002·Molecular Neurobiology·R Sattler, M Tymianski
Feb 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Michela FagioliniTakao K Hensch
Sep 18, 2003·The Journal of Biological Chemistry·Shigeyuki NadaTetsu Akiyama
Oct 8, 2003·Neuropharmacology·Lorraine V Kalia, Michael W Salter
Jan 27, 2004·The Journal of Biological Chemistry·Kate Prybylowski, Robert J Wenthold
Jan 30, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Maria A MorabitoLi-Huei Tsai
Sep 21, 2004·Nature Reviews. Neuroscience·Eunjoon Kim, Morgan Sheng
Oct 19, 2004·Oncogene·Lorraine V KaliaMichael W Salter
Dec 13, 2006·The European Journal of Neuroscience·Fabrizio GardoniMonica Di Luca

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Citations

Aug 21, 2013·Biological Trace Element Research·Wei QianZigui Zhang
Nov 24, 2011·Journal of Proteome Research·Min-Young SongKang-Sik Park
Oct 16, 2009·Proceedings of the National Academy of Sciences of the United States of America·Chad M PetitAndrew L Lee
Nov 22, 2011·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Ashish K RehniSandeep Arora
Oct 7, 2011·Clinical and Experimental Pharmacology & Physiology·Mohammed I HossainHeung-Chin Cheng
Mar 12, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Karen Perez de ArceAlejandra R Alvarez
Sep 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Qiu-Ju ZhuXiao-Yu Hou
Feb 18, 2016·Molecular Neurobiology·Daniela VallejoNibaldo C Inestrosa
Jul 18, 2014·Journal of Pharmacological Sciences·Norio Takagi
Apr 22, 2020·Advanced Therapeutics·Nikolaj R ChristensenKristian Strømgaard
May 26, 2009·Neuroscience Letters·Om Prakash MishraMaria Delivoria-Papadopoulos

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