PMID: 9648887Jul 2, 1998Paper

Regulation of Drosophila Ca2+/calmodulin-dependent protein kinase II by autophosphorylation analyzed by site-directed mutagenesis

Journal of Neurochemistry
Z WangL C Griffith

Abstract

In this study we demonstrate that Drosophila calcium/calmodulin-dependent protein kinase II (CaMKII) is capable of complex regulation by autophosphorylation of the three threonines within its regulatory domain. Specifically, we show that autophosphorylation of threonine-287 in Drosophila CaMKII is equivalent to phosphorylation of threonine-286 in rat alpha CaMKII both in its ability to confer calcium independence on the enzyme and in the mechanistic details of how it becomes phosphorylated. Autophosphorylation of this residue occurs only within the holoenzyme structure and requires calmodulin (CaM) to be bound to the substrate subunit. Phosphorylation of threonine-306 and threonine-307 in the CaM binding domain of the Drosophila kinase occurs only in the absence of CaM, and this phosphorylation is capable of inhibiting further CaM binding. Additionally, our findings suggest that phosphorylation of threonine-306 and threonine-307 does not mimic bound CaM to alleviate the requirement for CaM binding to the substrate subunit for intermolecular threonine-287 phosphorylation. These results demonstrate that the mechanism of regulatory autophosphorylation of this kinase predates the split between invertebrates and vertebrates.

Citations

Jun 16, 2001·The Journal of Biological Chemistry·P V SathyanarayananB W Poovaiah
Jul 13, 2002·Journal of Neurobiology·Demian ParkLeslie C Griffith
Feb 15, 2003·Archives of Insect Biochemistry and Physiology·Sandra Braak, Michael Fährmann
Sep 28, 2017·ELife·Gabriella Hannah WolffNicholas James Strausfeld
Jun 3, 2020·The Journal of Comparative Neurology·Francisco Javier MazaAlejandro Delorenzi
May 1, 2002·The Journal of Biological Chemistry·Zheng WangLeslie C Griffith
Nov 26, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Gabriella H Wolff, Nicholas J Strausfeld
Dec 31, 2003·The Journal of Biological Chemistry·Xiu Xia SunLeslie C Griffith
Mar 4, 2009·The Journal of Biological Chemistry·Haiqin LuBih-Hwa Shieh
Feb 5, 2000·Biochimica Et Biophysica Acta·V Iourgenko, L R Levin
Aug 2, 2006·Neuron·James J L HodgeLeslie C Griffith
Oct 28, 2009·Biochemical and Biophysical Research Communications·S Lynn BostromLeslie C Griffith

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