The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2 as interacting ligands

The Journal of Biological Chemistry
Kumlesh K DevJeremy M Henley

Abstract

The C terminus (ct) of protein kinase C-alpha (PKCalpha) has a type I PDZ binding motif, whereas GluR2 has a type II PDZ binding motif. Both motifs are recognized by the PDZ domain of protein interacting with protein kinase C (PICK1), and PICK1-PKCalpha-controlled phosphorylation regulates the synaptic expression and function of GluR2. Here, we show that a specific mutation within the carboxylate-binding loop of the PDZ domain of PICK1 (K27E; PICK1-KE) results in a loss of interaction with GluR2 but not with PKCalpha. In GST pull-down studies, PICK1-WT (wild type) but not PICK1-KE was retained by GST-ct-GluR2. Furthermore, PICK1-WT co-immunoprecipitated both PKCalpha and GluR2, whereas PICK1-KE only co-immunoprecipitated PKCalpha. In heterologous cells, PICK1-WT, but not PICK1-KE, clustered GluR2 and also clustered GluR1 in a GluR2-dependent manner. However, neither PICK1-WT nor PICK1-KE altered the distribution of PKCalpha, even after phorbol ester-induced redistribution of PKCalpha to the membrane. Finally, PICK1-KE showed no mislocalization when compared with PICK1-WT in neurons. Taken together, it appears that the PDZ domain of PICK1 is less sensitive to mutations for PKCalpha when compared with GluR2 binding. These results...Continue Reading

References

Jan 1, 1994·Annual Review of Neuroscience·M Hollmann, S Heinemann
Jan 7, 1993·Nature·T V Bliss, G L Collingridge
Jan 24, 1998·The Journal of Biological Chemistry·J StaudingerE N Olson
Aug 11, 1998·Neuron·A NishimuneJ M Henley
Jan 7, 2000·Biochemical and Biophysical Research Communications·R TakeyaH Sumimoto
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·H MizuguchiT Hayakawa
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·C H KimR L Huganir

❮ Previous
Next ❯

Citations

Dec 2, 2004·Nature Reviews. Drug Discovery·Kumlesh K Dev
Jun 1, 2010·Cell Communication and Signaling : CCS·Ho-Jin Lee, Jie J Zheng
Aug 31, 2011·PLoS Computational Biology·Iskra Staneva, Stefan Wallin
Dec 15, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ami CitriRobert C Malenka
Mar 13, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jang-Su ParkYuan-Xiang Tao
Jan 23, 2010·Molecular Pain·Yun WangLi Fang
Feb 26, 2013·Synapse·Marylène C Focant, Emmanuel Hermans
Mar 27, 2007·Protein Science : a Publication of the Protein Society·Jonathan M ElkinsDeclan A Doyle
Mar 19, 2005·The Journal of Biological Chemistry·Kenneth L MadsenUlrik Gether
Mar 3, 2010·Protein Science : a Publication of the Protein Society·Z Nevin Gerek, S Banu Ozkan
Apr 18, 2018·Current Neuropharmacology·David Agustín León-NavarroMairena Martín

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.