Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, REPLICATIVE LIFE-SPAN, AMINO-ACID SENSOR, PROTEIN-KINASE, SACCHAROMYCES-CEREVISIAE, FLUORESCENCE COMPLEMENTATION, STRESS RESISTANCE, BINDING-SITE, A PATHWAY, GAP1, ACTIVATION, Protein Kinase B, S6 kinase, Sch9, nutrient regulation, transceptor, yeast, Amino Acid Transport Systems, Binding Sites, Cation Transport Proteins, Citrulline, Mutation, Protein Interaction Domains and Motifs, Protein Interaction Maps, Protein Serine-Threonine Kinases, Proton-Phosphate Symporters, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, 03 Chemical Sciences, 06 Biological Sciences, 11 Medical and Health Sciences, 3101 Biochemistry and cell biology

Abstract:

Multiple starvation-induced, high-affinity nutrient transporters in yeast function as receptors for activation of the protein kinase A (PKA) pathway upon re-addition of their substrate. We now show that these transceptors may play more extended roles in nutrient regulation. The Gap1 amino acid, Mep2 ammonium, Pho84 phosphate and Sul1 sulfate transceptors physically interact in vitro and in vivo with the PKA-related Sch9 protein kinase, the yeast homolog of mammalian S6 protein kinase and protein kinase B. Sch9 is a phosphorylation target of TOR and well known to affect nutrient-controlled cellular processes, such as growth rate. Mapping with peptide microarrays suggests specific interaction domains in Gap1 for Sch9 binding. Mutagenesis of the major domain affects the upstart of growth upon the addition of L-citrulline to nitrogen-starved cells to different extents but apparently does not affect in vitro binding. It also does not correlate with the drop in L-citrulline uptake capacity or transceptor activation of the PKA target trehalase by the Gap1 mutant forms. Our results reveal a nutrient transceptor-Sch9-TOR axis in which Sch9 accessibility for phosphorylation by TOR may be affected by nutrient transceptor-Sch9 interaction under conditions of nutrient starvation or other environmental challenges.