Skip to content

Research at St Andrews

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

Research output: Contribution to journalArticlepeer-review

Author(s)

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

School/Research organisations

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.
Close

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

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. A role for inositol monophosphatase 1 (IMPA1) in salinity adaptation in the euryhaline eel (Anguilla anguilla)

    Kalujnaia, S., McVee, J., Kasciukovic, T., Stewart, A. J. & Cramb, G., Oct 2010, In: FASEB Journal. 24, p. 3981-3991 11 p.

    Research output: Contribution to journalArticlepeer-review

  2. Leptin and obesity

    Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T. & Isenovic, E. R., 30 Apr 2021, (Accepted/In press) In: Frontiers in Endocrinology.

    Research output: Contribution to journalReview articlepeer-review

  3. Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes

    Sobczak, A. I. S., Katundu, K. G. H., Phoenix, F. A., Khazaipoul, S., Yu, R., Lampiao, F., Stefanowicz, F., Blindauer, C. A., Pitt, S. J., Smith, T. K., Ajjan, R. A. & Stewart, A. J., 21 Mar 2021, In: Chemical Science. 12, 11, p. 4079-4093 15 p.

    Research output: Contribution to journalArticlepeer-review

  4. Ablation of Enpp6 results in transient bone hypomineralization

    Dillon, S., Suchacki, K., Hsu, S-N., Stephen, L. A., Wang, R., Cawthorn, W. P., Stewart, A. J., Nudelman, F., Morton, N. M. & Farquharson, C., Feb 2021, In: JBMR Plus. 5, 2, 11 p., e10439.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Feedforward and feedback regulation of the MAPK and PI3K oscillatory circuit in breast cancer

    Hu, H., Goltsov, A., Bown, J. L., Sims, A. H., Langdon, S. P., Harrison, D. J. & Faratian, D., Jan 2013, In: Cellular Signalling. 25, 1, p. 26-32 7 p.

    Research output: Contribution to journalArticlepeer-review

  2. Features of the reversible sensitivity-resistance transition in PI3K/PTEN/AKT signalling network after HER2 inhibition

    Goltsov, A., Faratian, D., Langdon, S. P., Mullen, P., Harrison, D. J. & Bown, J., Feb 2012, In: Cellular Signalling. 24, 2, p. 493-504 12 p.

    Research output: Contribution to journalArticlepeer-review

  3. Compensatory effects in the PI3K/PTEN/AKT signaling network following receptor tyrosine kinase inhibition

    Goltsov, A., Faratian, D., Langdon, S. P., Bown, J., Goryanin, I. & Harrison, D. J., Feb 2011, In: Cellular Signalling. 23, 2, p. 407-416 10 p.

    Research output: Contribution to journalArticlepeer-review

  4. ERK2 signalling from internalised epidermal growth factor receptor in broken A431 cells

    Xue, L. & Lucocq, J., May 1998, In: Cellular Signalling. 10, 5, p. 339-48 10 p.

    Research output: Contribution to journalArticlepeer-review

ID: 9718612

Top