ATP binding to a unique site in the type-1 S2- inositol 1,4,5-trisphosphate receptor defines susceptibility to phosphorylation by protein kinase A.

The Journal of Biological Chemistry
Larry E WagnerDavid I Yule

Abstract

The subtype- and splice variant-specific modulation of inositol 1,4,5-trisphosphate receptors (InsP3R) by interaction with cellular factors plays a fundamental role in defining the characteristics of Ca2+ release in individual cell types. In this study, we investigate the binding properties and functional consequences of the expression of a putative nucleotide binding fold (referred to as the ATPC site) unique to the S2- splice variant of the type-1 InsP3R (InsP3R-1), the predominant splice variant in peripheral tissue. A glutathione S-transferase fusion protein encompassing amino acids 1574-1765 of the S2- InsP3R-1 and including the glycine-rich motif Gly-Tyr-Gly-Glu-Lys-Gly bound ATP specifically as measured by fluorescent trinitrophenyl-ATP binding. This binding was completely abrogated by a point mutation (G1690A) in the nucleotide binding fold. The functional sensitivity of S2- InsP3R-1 constructs was evaluated in DT40-3KO-M3 cells, a null background for InsP3R, engineered to express muscarinic M3 receptors. The S2- InsP3R-1 containing the G1690A mutation was markedly less sensitive to agonist stimulation than wild type S2- InsP3R-1 or receptors containing a similar (Gly --> Ala) mutation in the established nucleotide bind...Continue Reading

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Citations

Feb 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tania SzadoH Llewelyn Roderick
Apr 24, 2009·The Journal of Biological Chemistry·Matthew J BetzenhauserDavid I Yule
Jul 18, 2009·The Journal of Biological Chemistry·Matthew J BetzenhauserDavid I Yule
Aug 8, 2007·Annual Review of Physiology·Yiping Rong, Clark W Distelhorst
Apr 13, 2007·Physiological Reviews·J Kevin FoskettDon-On Daniel Mak
Feb 9, 2008·Biochimica Et Biophysica Acta·Jiuyong Xie
Mar 20, 2014·Biochimica Et Biophysica Acta·Hristina IvanovaGeert Bultynck
Apr 11, 2015·Journal of Molecular Neuroscience : MN·Syed Zahid Ali ShahLifeng Yang
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Oct 22, 2008·Methods : a Companion to Methods in Enzymology·Matthew J BetzenhauserDavid I Yule
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Aug 21, 2013·The Journal of Biological Chemistry·Kamil J AlzayadyDavid I Yule
Nov 21, 2007·The Journal of Biological Chemistry·Zachary T SchugSuresh K Joseph
Nov 23, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Han-A ParkElizabeth A Jonas

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