Fig. 6.

Schematic representation of proposed GRP78 regulation by the IGF-1/ AKT/mTORC1 signaling axis in the absence of ER stress, in MEF cells either overexpressing (R+) or lacking (R−) IGF-1 receptor. A: In the presence of intact IGF-1R signaling, GRP78 expression is regulated by PI3K/AKT and mTORC1, and is downregulated in response to inhibitors of both. B: In the absence of IGF-1R, there is dramatically reduced AKT phosphorylation and GRP78 expression compared to R+ cells. However, protein translation is maintained via mTORC1 activity, likely driven by p-ERK1/2, which is maintained in the R− cells. Induction of the unfolded protein response (UPR) and GRP78 by ER stress is intact in both cell types.