Figure 5.
Overview of the PI3K/AKT/mTOR pathway. When activated via mutation, this pathway provides a constitutive cellular growth signal. PTEN is a central tumor suppressor upstream of PDK1/AKT. LKB1 can inhibit mTORC1 via AMPK and TSC signaling. mTORC2 activates AKT by phosphorylating the S473 residue, whereas PDK1 activates AKT by phosphorylating T308. Activation of both mTORC1 and mTORC2 are required for progression of nevi to melanoma. Canonical outputs of mTORC1 include S6K and 4E–BP1. Tumor suppressors: red, oncogenic effect: blue. RTK, receptor tyrosine kinase.