Simplified model for the intersection of signaling pathways regulating protein synthesis and degradation

Simplified model for the intersection of signaling pathways regulating protein synthesis and degradation. Arrows indicate activating events, whereas perpendicular lines indicate inhibitory events. The solid lines represent direct activation. The dashed lines represent indirect activation, whereby intermediate steps are involved but are not specified in this schematic. Protein synthesis is regulated by protein kinase B (Akt), p44/42 MAPK (ERK½), and AMP-activated protein kinase (AMPK), leading to activation of the downstream targets mammalian target of rapamycin (mTOR), glycogen synthase kinase-3β (GSK3β), MAPK-interacting kinases ½ (MNK½), p70S6 kinase (p70S6K), eIF4E-binding protein 1 (4EBP1), and eukaryotic initiation factors 2B and 4E (eIF2B and eIF4E). Conversely, Akt is responsible for the phosphorylation status of forkhead box protein (FoxO). If FoxO is phosphorylated by Akt, it leaves the nucleus and becomes inactive, thus preventing protein degradation. If Akt activity is suppressed, FoxO becomes dephosphorylated, translocates to the nucleus, and exerts its transcriptional effects on atrogenes to induce protein degradation through the ubiquitin/proteasome pathway. PI3K, phosphoinositide 3-kinase.

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Intracellular signaling pathways regulating net protein balance following diaphragm muscle denervation. (2011) Heather M. Argadine, et al. Am J Physiol Cell Physiol. 2011 Feb;300(2):C318-C327. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

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