Phosphorylated AKT and Phosphorylated Ribosomal Protein S6 (pAKT/pS6)

Cellular pAKT/pS6 refers to the phosphorylated forms of AKT (Protein Kinase B) and Ribosomal Protein S6, which serve as key pharmacodynamic biomarkers for the PI3K/AKT/mTOR signaling pathway (UniProt P31749, P62753). AKT is a serine/threonine kinase that is activated via phosphorylation at Thr308 and Ser473 by PDK1 and mTORC2, respectively, in response to PI3K signaling (PMID: 31023958). Ribosomal Protein S6 is a downstream component of the mTORC1 signaling axis, phosphorylated by p70S6 Kinase to regulate protein synthesis and cell size (PMID: 29101595). This pathway is frequently dysregulated in human cancers through gain-of-function mutations in PIK3CA or loss of the PTEN phosphatase, making pAKT and pS6 levels critical indicators of oncogenic activity and therapeutic response (PubMed: 24436015). Drugs such as alpelisib (PI3K inhibitor), capivasertib (AKT inhibitor), and everolimus (mTOR inhibitor) are used to suppress this signaling, with reductions in pAKT and pS6 levels serving as evidence of target engagement in clinical settings (FDA: Piqray, Truqap, Afinitor). Monitoring these markers is essential for patient stratification and for managing the metabolic side effects, such as hyperglycemia, that often accompany the inhibition of this central metabolic axis (PMID: 30215161). Because pAKT and pS6 are readouts of pathway activity rather than individual druggable molecules, they are primarily used in research and clinical diagnostics to evaluate the efficacy of upstream inhibitors.

Other names

Phospho-AKTPhospho-S6p-AKTp-S6PI3K/AKT/mTOR pathway markersPhosphorylated AKT (Ser473/Thr308)Phosphorylated Ribosomal Protein S6 (Ser235/236)

Inhibition of the PI3K/AKT/mTOR signaling cascade by small molecules or macrolides, which prevents the phosphorylation of AKT and S6 proteins, thereby suppressing cell growth and proliferation.