Holton ML, Wang W, Emerson M, Neyses L, Armesilla AL. Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways. World J Biol Chem 2010; 1(6): 201-208 [PMID: 21537369 DOI: 10.4331/wjbc.v1.i6.201]
Corresponding Author of This Article
Angel L Armesilla, PhD, Molecular Pharmacology Group, Department of Pharmacy, Research Institute in Healthcare Sciences, Room MA 228, School of Applied sciences, University of Wolverhampton, WV1 1SB, Wolverhampton, United Kingdom. a.armesilla@wlv.ac.uk
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World J Biol Chem. Jun 26, 2010; 1(6): 201-208 Published online Jun 26, 2010. doi: 10.4331/wjbc.v1.i6.201
Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways
Mary Louisa Holton, Weiguang Wang, Michael Emerson, Ludwig Neyses, Angel L Armesilla
Mary Louisa Holton, Angel L Armesilla, Molecular Pharmacology Group, Department of Pharmacy, Research Institute in Healthcare Sciences, Room MA 228, School of Applied sciences, University of Wolverhampton, WV1 1SB, Wolverhampton, United Kingdom
Weiguang Wang, Oncology Group, Research Institute in Healthcare Sciences, School of Applied Sciences, University of Wolverhampton, Wulfruna Street, WV1 1SB, Wolverhampton, United Kingdom
Michael Emerson, National Heart and Lung Institute, Imperial College London, Exhibition Road, SW7 2AZ, London, United Kingdom
Ludwig Neyses, Cardiovascular Research Group, Manchester Academic Health Science Centre, Biomedical Research Centre and School of Biomedicine, University of Manchester, M13 9PT, Manchester, United Kingdom
Author contributions: Holton ML and Armesilla AL wrote the manuscript; Wang W, Emerson M and Neyses L corrected and critically read the manuscript.
Supported by The Breast Cancer Campaign and the Research Institute in Healthcare Sciences (Armesilla AL); The Wellcome Trust (Emerson M)
Correspondence to: Angel L Armesilla, PhD, Molecular Pharmacology Group, Department of Pharmacy, Research Institute in Healthcare Sciences, Room MA 228, School of Applied sciences, University of Wolverhampton, WV1 1SB, Wolverhampton, United Kingdom. a.armesilla@wlv.ac.uk
Telephone: +44-1902-322756 Fax: +44-1902-323465
Received: May 18, 2010 Revised: June 22, 2010 Accepted: June 24, 2010 Published online: June 26, 2010
Abstract
Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular free calcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulin-dependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.
