Fig. 2

q depletion affects Akt activation. (A) Graphical scheme of the proposed effects that tRNA Q-modification may exert on the PI3K/Akt pathway. PI derivatives are phosphorylated by different PI3K to form PI-3,4,5-trisphosphate [PI(3,4,5)P3], which works as an anchorage for Akt and its upstream activating kinase, PI-dependent kinase-1 (PDK1). PI(3,4,5)P3 can be dephosphorylated by phosphatases such as PTEN. Recruitment of both Akt and PDK1 facilitates PDK1-mediated phosphorylation and subsequent activation of Akt. An increase in the activation of Akt was observed when cells were incubated in q-free medium (B,C). This result suggests that PI phosphatases encoded by Q-genes like PTEN may be downregulated in the absence of q. (B) Representative Western blots showing levels of p-Akt and total Akt in HeLa cells cultured in q-free medium in the presence (+ q) or absence (−q) of 500 nM q for 14 days. (C) Quantification of the ratio between p-Akt and total Akt. For gel source data, see Figure S3. Data represents the mean ± S.D. of five independent samples. Statistical differences were analysed by two-sample t-test (**P < 0.01).