title: Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways.
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.
authors.affiliation: 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.
authors.forename: Mary Louisa
authors.initials: ML
authors.lastname: Holton
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Emerson
authors.forename: Ludwig
authors.initials: L
authors.lastname: Neyses
authors.forename: Angel L
authors.initials: AL
authors.lastname: Armesilla