Premium
Ribosomal protein S 6 phosphorylation is controlled by TOR and modulated by PKA in C andida albicans
Author(s) -
Chowdhury Tahmeena,
Köhler Julia R.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13130
Subject(s) - biology , anabolism , ribosomal protein s6 , tor signaling , phosphorylation , biochemistry , signal transduction , downregulation and upregulation , ribosomal protein , amino acid , microbiology and biotechnology , corpus albicans , protein biosynthesis , protein kinase a , ribosome , protein phosphorylation , yeast , rna , gene
Summary TOR and PKA signaling pathways control eukaryotic cell growth and proliferation. TOR activity in model fungi, such as S accharomyces cerevisiae , responds principally to nutrients, e.g., nitrogen and phosphate sources, which are incorporated into the growing cell mass; PKA signaling responds to the availability of the cells' major energy source, glucose. In the fungal commensal and pathogen, C andida albicans , little is known of how these pathways interact. Here, the signal from phosphorylated ribosomal protein S 6 ( P ‐ S 6) was defined as a surrogate marker for TOR ‐dependent anabolic activity in C . albicans . Nutritional, pharmacologic and genetic modulation of TOR activity elicited corresponding changes in P ‐ S 6 levels. The P ‐ S 6 signal corresponded to translational activity of a GFP reporter protein. Contributions of four PKA pathway components to anabolic activation were then examined. In high glucose concentrations, only T pk2 was required to upregulate P ‐ S 6 to physiologic levels, whereas all four tested components were required to downregulate P ‐ S 6 in low glucose. TOR was epistatic to PKA components with respect to P ‐ S 6. In many host niches inhabited by C . albicans , glucose is scarce, with protein being available as a nitrogen source. We speculate that PKA may modulate TOR ‐dependent cell growth to a rate sustainable by available energy sources, when monomers of anabolic processes, such as amino acids, are abundant.