Cell-to-cell variability in PI3K protein level regulates PI3K-AKT pathway activity in cell populations
Class Ia Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
Given that the PI3K pathway is one of the most frequently upregulated pathways in cancer, we propose that heterogeneity in PI3K activity is beneficial to normal tissues by restricting PI3K activation to only a subset of cells. This may serve to protect the population as a whole from overactivating the pathway, which can lead to cellular senescence or cancer. Consistent with this, we show that oncogenic mutations in p110α (H1047R and E545K) partially evade this negative regulation, resulting in increased AKT activity in the population.