IP3K (inositol 1,4,5-trisphosphate 3-kinase) catalyses the Ca2+-regulated phosphorylation of the second messenger Ins(1,4,5)P3, thereby inactivating the signal to release Ca2+ and generating Ins(1,3,4,5)P4. Here we have investigated the localization and activity of IP3KB and its modulation by proteolysis. We found that the N- and C-termini (either side of residue 262) of IP3KB localized predominantly to the actin cytoskeleton and ER (endoplasmic reticulum) respectively, both in COS-7 cells and in primary astrocytes. The functional relevance of this was demonstrated by showing that full-length (actin-localized) IP3KB abolished the histamine-induced Ca2+ response in HeLa cells more effectively than truncated constructs localized to the ER or cytosol. The superior efficacy of full-length IP3KB was also attenuated by disruption of the actin cytoskeleton. By transfecting COS-7 cells with double-tagged IP3KB, we show that the translocation from actin to ER may be a physiologically regulated process caused by Ca2+-modulated constitutive proteolysis in intact cells.
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December 2005
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Research Article|
December 06 2005
Regulation of the localization and activity of inositol 1,4,5-trisphosphate 3-kinase B in intact cells by proteolysis
Jowie C. H. Yu;
Jowie C. H. Yu
*Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Samantha M. Lloyd-Burton;
Samantha M. Lloyd-Burton
*Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Robin F. Irvine;
Robin F. Irvine
1
*Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
1To whom correspondence should be sent (email [email protected]).
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Michael J. Schell
Michael J. Schell
†Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, U.S.A.
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Publisher: Portland Press Ltd
Received:
May 19 2005
Revision Received:
September 20 2005
Accepted:
September 21 2005
Accepted Manuscript online:
September 21 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 392 (3): 435–441.
Article history
Received:
May 19 2005
Revision Received:
September 20 2005
Accepted:
September 21 2005
Accepted Manuscript online:
September 21 2005
Citation
Jowie C. H. Yu, Samantha M. Lloyd-Burton, Robin F. Irvine, Michael J. Schell; Regulation of the localization and activity of inositol 1,4,5-trisphosphate 3-kinase B in intact cells by proteolysis. Biochem J 15 December 2005; 392 (3): 435–441. doi: https://doi.org/10.1042/BJ20050829
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