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.
this identifier to cite or link
to this item:
|Title: ||The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit.|
|Citation: ||The Journal of Biological Chemistry, 280(33): 29479-29487|
|Publisher: ||American Society for Biochemistry and Molecular Biology|
|Issue Date: ||2005 |
|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.|
|Keywords: ||Sarcolemmal calcium Pump|
|Appears in Collections: ||Molecular Pharmacology Research Group|
|Files in This Item:|
|Related articles on PubMed|
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
The sarcolemmal calcium pump, alpha-1 syntrophin, and neuronal nitric-oxide synthase are parts of a macromolecular protein complex.
Williams JC, Armesilla AL, Mohamed TM, Hagarty CL, McIntyre FH, Schomburg S, Zaki AO, Oceandy D, Cartwright EJ, Buch MH, Emerson M, Neyses L
2006 Aug 18
|See all 263 articles|
All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.