Using yeast to uncover the regulation of protein kinase Cδ by ceramide

Cláudia Bessa, Clara Pereira, Mariana Leão, Cláudia Maciel, Sara Gomes, Jorge Gonçalves, Manuela Corte-Real, Vítor Costa, Lucília Saraiva

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3 Citations (Scopus)

Abstract

The regulation of protein kinase C (PKC) isoforms by ceramide is still controversial. In this work, the yeast Saccharomyces cerevisiae was used as a model to elucidate the effect of ceramide on the activity of mammalian PKC isoforms. For that, isc1Δ cells, with a deletion in the pathway for ceramide production by hydrolysis of complex sphingolipids, individually expressing mammalian PKCα, δ and ζ were used. Contrary to PKCα and ζ, expression of PKCδ in isc1Δ cells exhibited a similar phenotype to that observed with wild-type yeast cells expressing PKCδ treated with a PKC activator, as phorbol 12-myristate 13-acetate (PMA), specifically a growth inhibition associated with a G2/M cell cycle arrest. Interestingly, in isc1Δ yeast cells expressing PKCδ this phenotype was completely abrogated in the presence of exogenous ceramide. Moreover, using a yeast-based assay previously developed for the screening of PKC inhibitors, it was also shown that, like the known PKC inhibitor NPC 15437, ceramide reduced the PMA-induced growth inhibition, supporting an inhibitory effect of ceramide on PKCδ. Altogether, these results may indicate that ceramide distinctly interfere with the activity of PKCα, δ and ζ. Most importantly, they showed that ceramide is an inhibitor of PKCδ.

Original languageEnglish
Pages (from-to)700-705
Number of pages6
JournalFEMS Yeast Research
Volume13
Issue number7
DOIs
Publication statusPublished - 1 Nov 2013

Keywords

  • Ceramide
  • Protein kinase Cδ
  • Saccharomyces cerevisiae

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    Bessa, C., Pereira, C., Leão, M., Maciel, C., Gomes, S., Gonçalves, J., Corte-Real, M., Costa, V., & Saraiva, L. (2013). Using yeast to uncover the regulation of protein kinase Cδ by ceramide. FEMS Yeast Research, 13(7), 700-705. https://doi.org/10.1111/1567-1364.12069