In healthy animal tissue, cells proliferate with a remarkably consistent size at division, demonstrating tight coordination between cell growth and division within specific environmental contexts. By contrast, cell proliferation ceases in nutrient-starved conditions in order to conserve energy, maintain homeostasis and ensure survival. When nutrient supply is abundant, cells maintain high levels of protein synthesis to increase biomass and support cell division. Reduced phosphorylation of the MAPKK Byr1, at a site whose human equivalent controls docking between MEK and ERK, prevented sexual differentiation when resources were sparse but not eliminated.Īll eukaryotic cells are exquisitely sensitive to changes in their external environments and constantly adapt their metabolism and rate of division to meet dynamic changes in nutrient availability. Nutritional control of gene expression was reflected in multiple targets in RNA metabolism, while significant modulation of actin cytoskeletal components points to adaptations in morphogenesis and cell integrity networks. Using a yeast strain with an ATP analogue-sensitized Cdc2 kinase, we excluded sites that were changed as an indirect consequence of mitotic control modulation by nitrogen stress or TOR signalling. Elimination of AMPK inhibition of TORC1, by removal of AMPK α ( ssp2::ura4 +), identified phosphosites where nitrogen stress-induced changes were independent of TOR control. One hundred and thirty of these sites were regulated by both perturbations, and the majority of these (119) new targets have not previously been linked to either nutritional or TOR control in either yeasts or humans. Phosphorylation levels at more than 1000 sites were altered following nitrogen stress or Torin1 inhibition of the TORC1 and TORC2 networks that comprise TOR signalling. We have applied quantitative, SILAC mass spectrometry to map TOR and nutrient-controlled signalling in the fission yeast Schizosaccharomyces pombe. Fluctuations in TOR, AMPK and MAP-kinase signalling maintain cellular homeostasis and coordinate growth and division with environmental context.
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