Causal metabolic signals and functionality of protein phosphorylation in TOR signaling identified
In two related dynamic omics studies, researchers from the Aebersold and Sauer lab identified causal metabolic signals and functionality of protein phosphorylation in TOR signaling.
Cells react to nutritional cues in changing environments via the integrated action of signaling, transcriptional, and metabolic networks. Mechanistic insight into signaling processes is often complicated because ubiquitous feedback loops obscure causal relationships. Consequently, the endogenous inputs of many nutrient signaling pathways and the functionality of the many phosphorylation sites remain unknown. In the context of the SystemsX.ch projects YeastX and SignalX, we analyzed the dynamic regulation of nitrogen metabolism by the target of rapamycin complex 1 (TORC1) pathway in budding yeast through dynamic transcriptomic, proteomic, phosphoproteomic, and metabolomic measurements. Multi-level integration of dynamic data with a probabilistic, model-based method, developed by the Stelling lab, inferred causal relationships between metabolism, signaling, and gene regulation. Through consistency of early phosphorylation events during shifts in nitrogen sources and rapamycin treatment, we identified 51 candidate and 10 known proximal targets of TORC1. By correlating these phosphoproteomics data with dynamic metabolomics data, we further inferred the functional role of phosphorylation on the metabolic activity of 12 enzymes, including three candidate TORC1-proximal targets in nucleotide, amino acid, and carbohydrate metabolism.
References:
external pageDynamic phosphoproteomics reveals TORC1-dependent regulation of yeast nucleotide and amino acid biosynthesis. Oliveira AP, Ludwig C, Zampieri M, Weisser H, Aebersold R, Sauer U. 2015. Sci Signal. 8(374):rs4.
external pageInferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome. Oliveira AP, Dimopoulos S, Busetto AG, Christen S, Dechant R, Falter L, Haghir Chehreghani M, Jozefczuk S, Ludwig C, Rudroff F, Schulz JC, González A, Soulard A, Stracka D, Aebersold R, Buhmann JM, Hall MN, Peter M, Sauer U, Stelling J. 2015. Mol Syst Biol. 11:802.
