Translation inhibitors in chronically activated PDGFRA cells

Chronic stimulation of the PDGFRA receptor results in decreased phosphorylation of RSK1/2 and S6K1/2, which subsequently impairs the phosphorylation of S6 ribosome protein and associated ribosome biogenesis and 5′ TOP mRNA translation. The phosphorylation of 4EBP1 and PDCD4 are suppressed, which subsequently limits the components of the eIF4F complex (eIF4E and eIF4A) from joining into the complex. In addition, the phosphorylation of the translation initiation factor eIF4B is also decreased. These changes result in a suppressed CAP-dependent translation initiation in cells with chronic stimulated PDGFRA signaling compared with acute stimulated ones. Based on figure S7 from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238596/ Zhou et al]. Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.

慢性刺激PDGFRA受体导致RSK1/2和S6K1/2的磷酸化水平降低，进而损害S6核糖体蛋白的磷酸化和相关的核糖体生物合成以及5' TOP mRNA的翻译。4EBP1和PDCD4的磷酸化受到抑制，从而限制了eIF4F复合物（eIF4E和eIF4A）的组成成分结合成复合物。此外，翻译起始因子eIF4B的磷酸化也减少。这些变化导致与急性刺激相比，慢性刺激PDGFRA信号通路细胞的CAP依赖性翻译起始受到抑制。基于Zhou等人提供的图S7 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238596/]。基于PhosphoSitePlus（R），www.phosphosite.org的信息添加了蛋白质磷酸化位点。