Figure 4

Crosstalk among Wnt, insulin, and FOXO signaling cascades. TCF and FOXO compete with each other for a limited pool of free β-cat. Aging and oxidative stress shift the balance in favor of FOXO signaling via JNK to activate downstream FOXO target genes. Contrastingly, insulin and growth factors shift the balance in favor of Wnt/TCF signaling by facilitating the nuclear exclusion of FOXO via PKB/SGK as well as by activating β-cat, thus resulting in the activation of downstream Wnt target genes. PKB, protein kinase B. ROS, reactive oxygen species. JNK, c-Jun N-terminal kinase. FOXO, forkhead box O. SGK, serum and glucocorticoid kinase.