Figure 8: Overview of the cytosolic translation regulatory network anchored on three major protein kinases, TOR, SnRKs and GCN2.

(Left) Four TOR outputs. (i) TOR triggers phosphorylation of the h subunit of eIF3 through the S6 kinase. This event supports the role of eIF3h in reinitiation after uORF translation. It is triggered by light stimulated synthesis of auxin and subsequent activation of TOR by the Rho-like small G protein (ROP2). (ii) Phosphorylation of the RNA polymerase III repressor protein, Maf1, boosts synthesis of tRNAs and rRNAs. (iii) TOR induces the phosphorylation of ribosomal protein eS6 through the S6 kinase, although the biochemical significance of this event remains unknown. (iv) TOR phosphorylation of MRF proteins through S6 kinase triggers MRF1 association with eIF4A and activates translation. (v) Sulfur deficiency depletes TOR activity, possibly via low glucose and SnRK signaling.

(Middle) Interaction of SnRKs and TOR. (i) Under conditions of low energy, active SnRK1 may phosphorylate Raptor1B, which may trigger disassembly of the active TOR complex and translational inhibition. High energy signals such as trehalose-6-phosphate, glucose −6 or −1-phosphate inhibit repression of SnRK1 on TOR complex. (ii) ABA also activates SnRK1 via its negative regulator, protein phosphatase 2C (PP2C). (iii) SnRK2 is activated by ABA under abiotic stress conditions and may likewise lead to Raptor phosphorylation. SnAK is the SnRK activating kinase whose binding to SnRK is inhibited by T6P. Other phosphorylation targets of SnRK are listed in Table 1.

(Right) GCN2 kinase is co-activated by GCN1 and uncharged tRNA. GCN2 phosphorylates the α subunit of the GTPase eIF2. GCN2 is activated by multiple abiotic and biotic stressors, some of which may deplete amino acids and increase deacylated tRNAs. Depletion of O-acetyl serine, a precursor of cysteine, stimulates GCN2. Reactive oxygen species (ROS) arise from the photosynthetic apparatus under excess light and activate GCN2. ROS also accompany many of the other triggers known to activate GCN2 such as herbicide and cold.

Black arrows and red T-bars represent activation or inhibition, respectively. Dashed lines indicate indirect or hypothetical connections. Based on Schepetilnikov et al., 2013 and 2017, Rodrigues et al., 2013; Nukarinen, 2016; Lee and Pai, 2017; Izquierdo et al., 2018; Ahn and Pai, 2019; Van Leene et al., 2019, Wang et al., 2018, Rodriguez et al., 2019, Dong et al., 2017, Lageix et al., 2008, Wang et al., 2018, Lokdarshi et al., 2020a, Lokdarshi et al., 2020b.