FIG. 9.

Redox regulation of the PI3K/Akt signaling pathway. PI3K/Akt transduces the signal for cell survival mainly through phosphorylation of target molecules by Akt. This results in inactivation of proapoptotic proteins and activation of transcription factors, which target antiapoptotic proteins. Under oxidative stress, this pathway is activated by oxidative inactivation of phosphatases [i.e., protein tyrosine phosphatases (PTPases) and PTEN], allowing constitutive activation of tyrosine kinase receptor and PI3K. However, direct oxidative modification of PI3K and Akt can result in their inactivation and compromise the survival signals. Furthermore, the PI3K/Akt pathway can also promote cellular production of ROS through activation of Rac and NADPH oxidase (NOX). *Site of redox regulation. Grey, Active forms of the proteins; TORC2, mTOR complex 2.