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. 2021 Sep 23;9:745670. doi: 10.3389/fcell.2021.745670

FIGURE 3.

FIGURE 3

Insulin like growth factor 1 (IGF1) signaling is an important regulator of epidermal homeostasis (created with biorender.com). Binding of IGF1 activates the IGF1R and the downstream PI3K/AKT signaling cascade via the phosphorylation of its components PI3K, AKT, mTOR, and S6K, resulting in increased proliferation and cell cycle progression as well as decreased apoptosis. Activated AKT2 phosphorylates PKP1, which translocates from the cell membrane to the cytoplasm. Phosphorylated cytoplasmic PKP1 is stabilized and protected from degradation via 14-3-3γ binding, resulting in impaired adhesion but increased proliferation, migration and anchorage independent growth. mTOR and S6K regulate binding of translation initiation factors of the eIF4 complex to mRNAs, thereby promoting protein biosynthesis. Phosphorylated PKP1 interacts with this translation initiation complex and stimulates eIF4A activity thereby facilitating unwinding of secondary structures in the 5′-UTR. The increase in protein biosynthesis correlates with increased proliferation and cell growth.