Using yeast to uncover the regulation of protein kinase C delta by ceramide

作者：Bessa Claudia; Pereira Clara; Leao Mariana; Maciel Claudia; Gomes Sara; Goncalves Jorge; Corte Real Manuela; Costa Vitor; Saraiva Lucilia^*

来源：FEMS Yeast Research, 2013, 13(7): 700-705.

DOI：10.1111/1567-1364.12069

• protein kinase C
• ceramide
• Saccharomyces cerevisiae

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, isc1 cells, with a deletion in the pathway for ceramide production by hydrolysis of complex sphingolipids, individually expressing mammalian PKC, and were used. Contrary to PKC and , expression of PKC in isc1 cells exhibited a similar phenotype to that observed with wild-type yeast cells expressing PKC 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 isc1 yeast cells expressing PKC 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 PKC. Altogether, these results may indicate that ceramide distinctly interfere with the activity of PKC, and . Most importantly, they showed that ceramide is an inhibitor of PKC.

• 出版日期2013-11