PMID: 9024696Feb 10, 1997

GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules

The Journal of Cell Biology
Eunjoon KimM Sheng


The molecular mechanisms underlying the organization of ion channels and signaling molecules at the synaptic junction are largely unknown. Recently, members of the PSD-95/SAP90 family of synaptic MAGUK (membrane-associated guanylate kinase) proteins have been shown to interact, via their NH2-terminal PDZ domains, with certain ion channels (NMDA receptors and K+ channels), thereby promoting the clustering of these proteins. Although the function of the NH2-terminal PDZ domains is relatively well characterized, the function of the Src homology 3 (SH3) domain and the guanylate kinase-like (GK) domain in the COOH-terminal half of PSD-95 has remained obscure. We now report the isolation of a novel synaptic protein, termed GKAP for guanylate kinase-associated protein, that binds directly to the GK domain of the four known members of the mammalian PSD-95 family. GKAP shows a unique domain structure and appears to be a major constituent of the postsynaptic density. GKAP colocalizes and coimmunoprecipitates with PSD-95 in vivo, and coclusters with PSD-95 and K+ channels/NMDA receptors in heterologous cells. Given their apparent lack of guanylate kinase enzymatic activity, the fact that the GK domain can act as a site for protein-protein...Continue Reading


Oct 12, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S D DimitratosP J Bryant
Sep 19, 2000·The Journal of Comparative Neurology·S LeeR J Dunn
Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A W WolkoffB F Scharschmidt
Jul 26, 2006·Cell and Tissue Research·Tobias M Boeckers
Sep 21, 2013·Molecules and Cells·Inna V NechipurenkoPiali Sengupta
May 17, 2005·Molecular and Cellular Neurosciences·Ronald S PetraliaRobert J Wenthold
Apr 29, 2005·Brain Research. Molecular Brain Research·Zhang Jing-PingTatsuo Suzuki
Feb 19, 2013·Psychiatry Research·Jun-Ming LiChia-Hsiang Chen
Jun 21, 2002·Biochemical and Biophysical Research Communications·Minji KimTetsu Akiyama
Aug 12, 1999·European Journal of Pharmacology·F CattabeniM Di Luca
Dec 12, 2002·Progress in Biophysics and Molecular Biology·L González-MariscalB E Jaramillo
Aug 12, 2003·Cell Calcium·Mark Arundine, Michael Tymianski
Jun 17, 1999·Trends in Neurosciences·D Van Rossum, U K Hanisch
Nov 27, 1998·Neuroscience Research·Y HataY Takai
May 29, 2000·Neuroscience Letters·X LuM Baudry
Aug 15, 2002·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Yang Z HuangLin Mei
Mar 8, 2002·Cellular Signalling·Eun Mi Hur, Kyong Tai Kim
Apr 21, 1999·Current Opinion in Cell Biology·J H Kim, R L Huganir
Feb 19, 2000·Current Opinion in Neurobiology·S H Lee, Morgan Sheng
Sep 27, 2002·Current Opinion in Pharmacology·Hans-Jürgen Kreienkamp
Nov 22, 2005·Nature Cell Biology·Nathalie SansRobert J Wenthold
Sep 21, 2004·Nature Reviews. Neuroscience·Eunjoon Kim, Morgan Sheng
Jan 21, 2009·Nature Reviews. Neuroscience·Wei Feng, Mingjie Zhang
Jan 16, 2007·Nature Structural & Molecular Biology·Michael L ReeseVolker Dötsch
Apr 12, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·K HiraoY Takai
Oct 13, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·H YanaiT Akiyama
Dec 21, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·K HaraguchiT Akiyama
Jun 13, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Badal C RoyTetsu Akiyama
Jun 26, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kazuyoshi KohuTetsu Akiyama
Oct 31, 2002·The European Journal of Neuroscience·Nikolaj KlöckerDavid S Bredt


May 13, 1977·Brain Research·G A Banker, W M Cowan
Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·P RuffA Husain-Chishti
Jan 1, 1993·Annual Review of Neuroscience·S C Froehner
Jan 27, 1995·Cell·G B CohenD Baltimore
Feb 13, 1995·FEBS Letters·U KistnerM Linial
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·R A LueA H Chishti
Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·E WillottJ M Anderson
Apr 1, 1996·Current Biology : CB·J M Anderson
Oct 1, 1996·Current Opinion in Neurobiology·M Sheng, Eunjoon Kim

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