A mammalian phospholipase A2 in yeast: a global view.
Mojca Mattiazzi (1), Uros Petrovi č (1), Joseph L. DeRisi (2), Igor Krizaj (1)
(1) Biochem. and Mol. Biol., Jozef Stefan Institute, Jamova 39, Ljubljana, SI-1000, Slovenia; (2) University of California, San Francisco, CA, USA
Secretory phospholipases A2 are mammalian enzymes involved in a wide range of (patho)physiological processes such as inflammation, apoptosis, tumour resistance and neurotoxicity. Ammodytoxin is a secretory phospholipase A2 from the venom of the long-nosed viper ( Vipera ammodytes ammodytes ). Its cellular targets include 14-3-3 proteins and calmodulin, both evolutionarily highly conserved regulatory proteins present in all eukaryotic cells. Our laboratory has been using S. cerevisiae as a model to study the molecular mechanism of the cellular effects of secretory phospholipases A2 , with ammodytoxin as a representative molecule. Because of its several molecular targets, ammodytoxin is a multifunctional protein, consequently to assess the molecular mechanisms of its effects, a global approach was required. We have performed DNA microarray transcriptional analysis in response to ammodytoxin expression in yeast and synthetic genetic array analysis to identify all genetic interactions of the ammodytoxin gene with the yeast genome. Data from these experiments will be presented and interpreted in terms of the possible molecular mechanism of action of secretory phospholipases A2 in mammals. While some results are in accordance with previous findings, others open a whole new set of fascinating possibilities. Moreover, our results point to a potential role of phospholipases A2 in yeast physiology.