Format

Send to

Choose Destination
FEMS Yeast Res. 2013 Nov;13(7):700-5. doi: 10.1111/1567-1364.12069. Epub 2013 Sep 9.

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

Author information

1
REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.

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.

KEYWORDS:

Saccharomyces cerevisiae; ceramide; protein kinase Cδ

PMID:
23937324
DOI:
10.1111/1567-1364.12069
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for Wiley
Loading ...
Support Center