Fig. 2: PI3K/AKT activation promotes PPP by stabilizing G6PD.

a, b The enzymatic activities and protein levels of G6PD were increased in the Pten null, CS and GE mES cells compared with the WT cells, and decreased after PKI-587 (1 µM) treatment in the Pten null mES cells. c PPP metabolites and nucleotide production were decreased by PKI-587 or 6-AN treatment. The Pten null mES cells were switched to medium containing [U-¹³C] glucose and continuously cultured for 12 h, with or without PKI-587 (1 µM) or 6-AN (100 nM) for the indicated time periods. d The half-lives of G6PD in the Pten WT and null mES cells were measured after PKI-587 (1 µM) or vehicle treatment for 24 h, or treatment with CHX (100 µg/ml) for the indicated time periods. e PTEN controls ubiquitination-mediated degradation of the endogenous G6PD. PTEN WT and null HEK293T cells were transfected with the HA-Ubiquitin expression plasmids. Twenty-four hours later, cells were incubated with or without MG132 (5 μM) or PKI-587 (1 µM) for 24 h. Total cell lysates were immunoprecipitated with an anti-G6PD antibody. f HEK293T cells were cotransfected with the HA-ubiquitin, Flag-G6PD WT or Flag-G6PD K8R expression plasmids. Twenty-four hours later, the cells were incubated with or without MG132 (5 µM) for 16 h. Total cell lysates were harvested, immunoprecipitated with a Flag antibody. g The half-lives of exogenous WT and K8R G6PD were measured after CHX (100 µg/ml) treatment for the indicated time periods. Data are presented as the mean ± SD and compared with the WT or untreated cells. n = 3, each experiment was performed four independent times. *p < 0.05, **p < 0.001, and ***p < 0.001, based on Student’s t test (two-sided ANOVA). See also Supplementary Fig. 2 and Supplementary Table 1. Source data are provided as a Source Data file.