1887

Abstract

The phosphatidylinositol (PtdIns) 3-kinase Vps34p of the human pathogenic yeast participates in virulence and in protein transport. In order to dissect these two functions, a search for proteins interacting with Vps34p was performed using a yeast two-hybrid system. This study demonstrates the physical interaction between Vps34p and Ade5,7p, which is the bifunctional enzyme of the purine nucleotide biosynthetic pathway. The interaction initially observed in a yeast two-hybrid system was confirmed with recombinant proteins. Given the complex formation between Ade5,7p and the virulence-regulating Vps34p, it was of interest to characterize the function of Ade5,7p in . To this end, , null mutants were generated. The resulting mutants were adenine deficient, and sensitive to the presence of metal ions. In addition, the , null mutants were avirulent in a mouse model of systemic candidiasis, and showed reduced hyphal growth in an agar matrix under embedded conditions. In summary, Ade5,7p interacts with the multifunctional virulence regulator PtdIns 3-kinase Vps34p, and , and null mutant strains show similar phenotypes regarding sensitivity to metal ions, hyphal growth and virulence.

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2007-07-01
2019-10-22
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