University of Wolverhampton
Browse
Collection All
bullet
bullet
bullet
bullet
Listed communities
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet

Wolverhampton Intellectual Repository and E-Theses > Research Institutes > Research Institute in Healthcare Science > Molecular Pharmacology Research Group > The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/7700
    Del.icio.us     LinkedIn     Citeulike     Connotea     Facebook     Stumble it!



Title: The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit.
Authors: Buch, Mamta H.
Pickard, Adam
Rodriguez, Antonio
Gillies, Sheona
Maass, Alexander H.
Emerson, Michael
Cartwright, Elizabeth J.
Williams, Judith C.
Oceandy, Delvac
Redondo, Juan Miguel
Neyses, Ludwig
Armesilla, Angel Luis
Citation: The Journal of Biological Chemistry, 280(33): 29479-29487
Publisher: American Society for Biochemistry and Molecular Biology
Issue Date: 2005
URI: http://hdl.handle.net/2436/7700
DOI: 10.1074/jbc.M501326200
PubMed ID: 15955804
Additional Links: http://www.jbc.org/cgi/reprint/280/33/29479
Abstract: The calcineurin/nuclear factor of activated T-cell (NFAT) pathway represents a crucial transducer of cellular function. There is increasing evidence placing the sarcolemmal calcium pump, or plasma membrane calcium/calmodulin ATPase pump (PMCA), as a potential modulator of signal transduction pathways. We demonstrate a novel interaction between PMCA and the calcium/calmodulin-dependent phosphatase, calcineurin, in mammalian cells. The interaction domains were located to the catalytic domain of PMCA4b and the catalytic domain of the calcineurin A subunit. Endogenous calcineurin activity, assessed by measuring the transcriptional activity of its best characterized substrate, NFAT, was significantly inhibited by 60% in the presence of ectopic PMCA4b. This inhibition was notably reversed by the co-expression of the PMCA4b interaction domain, demonstrating the functional significance of this interaction. PMCA4b was, however, unable to confer its inhibitory effect in the presence of a calcium/calmodulin-independent constitutively active mutant calcineurin A suggesting a calcium/calmodulin-dependent mechanism. The modulatory function of PMCA4b is further supported by the observation that endogenous calcineurin moves from the cytoplasm to the plasma membrane when PMCA4b is overexpressed. We suggest recruitment by PMCA4b of calcineurin to a low calcium environment as a possible explanation for these findings. In summary, our results offer strong evidence for a novel functional interaction between PMCA and calcineurin, suggesting a role for PMCA as a negative modulator of calcineurin-mediated signaling pathways in mammalian cells. This study reinforces the emerging role of PMCA as a molecular organizer and regulator of signaling transduction pathways.
Type: Article
Language: en
Keywords: Sarcolemmal calcium Pump
T-cell pathway
Plasma Membrane
PMCA4b
ISSN: 0021-9258
Appears in Collections: Molecular Pharmacology Research Group

Files in This Item:
File Description Size Format View/Open
Armesilla4.pdf372KbAdobe PDFThumbnail
View/Open

Related articles on PubMed
bullet
Novel functional interaction between the plasma membrane Ca2+ pump 4b and the proapoptotic tumor suppressor Ras-associated factor 1 (RASSF1).
Armesilla AL, Williams JC, Buch MH, Pickard A, Emerson M, Cartwright EJ, Oceandy D, Vos MD, Gillies S, Clark GJ, Neyses L
2004 Jul 23
bullet
bullet
bullet
Two-site interaction of nuclear factor of activated T cells with activated calcineurin.
Garcia-Cozar FJ, Okamura H, Aramburu JF, Shaw KT, Pelletier L, Showalter R, Villafranca E, Rao A
1998 Sep 11
bullet
Endothelial nitric oxide synthase activity is inhibited by the plasma membrane calcium ATPase in human endothelial cells.
Holton M, Mohamed TM, Oceandy D, Wang W, Lamas S, Emerson M, Neyses L, Armesilla AL
2010 Aug 1
See all 118 articles

All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Fairtrade - Guarantees a better deal for Third World Producers

University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY

Course enquiries: 0800 953 3222, General enquiries: 01902 321000,
Email: enquiries@wlv.ac.uk | Freedom of Information | Disclaimer and copyright | Website feedback | The University as a charity

OR Logo Powered by Open Repository | Cookies