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Phospholipase C-η2 is activated by elevated intracellular Ca2+ levels.

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Author(s)

Petra Popovics, William Beswick, Simon Guild, Gordon Cramb, Kevin Morgan, Robert P. Millar, Alan J. Stewart

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Abstract

Phospholipase C-η2 (PLCη2) is a novel enzyme whose activity in a cellular context is largely uncharacterised. In this study the activity of PLCη2 was examined via [3H]inositol phosphate release in COS7 cells expressing the enzyme. PLCη2 activity increased approximately 5-fold in response to monensin, a Na+/H+ antiporter. This was significantly inhibited by CGP-37157 which implies that the effect of monensin was due, at least in part, to mitochondrial Na+/Ca2+-exchange. Direct activation of PLCη2 by <1 μM Ca2+ was confirmed in permeabilised transfected cells. The roles of the PH and C2 domains in controlling PLCη2 activity via membrane association were also investigated. A PH domain-lacking mutant exhibited no detectable activity in response to monensin or Ca2+ due to an inability to associate with the cell membrane. Within the C2 domain, mutation of D920 to alanine at the predicted Ca2+-binding site dramatically reduced enzyme activity highlighting an important regulatory role for this domain. Mutation of D861 to asparagine also influenced activity, most likely due to altered lipid selectivity. Of the C2 mutations investigated, none altered sensitivity to Ca2+. This suggests that the C2 domain is not responsible for Ca2+ activation. Collectively, this work highlights an important new component of the Ca2+ signalling toolkit and given its sensitivity to Ca2+, this enzyme is likely to facilitate the amplification of intracellular Ca2+ transients and/or crosstalk between Ca2+-storing compartments in vivo.
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Details

Original languageEnglish
Pages (from-to)1777-1784
Number of pages8
JournalCellular Signalling
Volume23
Issue number11
Early online date29 Jun 2011
DOIs
Publication statusPublished - 1 Nov 2011

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