Fig. 1

Regulation of mTORC1 by growth factors. Activation of the IR and IGF-1R leads to phosphorylation of the IRS which subsequently activate PI3K. PI3K generates PIP3 which recruits PDK1 and Akt to the plasma membrane. Akt is then activated by PDK1 and mTORC2. Activated Akt then inhibits several substrates, namely the TSC-TBC complex which functions as a negative regulator of mTORC1, GSK3 β which degrades β-catenin, FoxO3a which stimulates MuRF1 and MAFbx and PRAS40 which inhibits mTORC1. Akt activation is also induced by androgens, possibly by enhancing PI3K activity and mediated by GPCR6A. Additionally, Akt activation is inhibited by activation of ActRII receptors through activation of Smad2 and Smad3