Figure 4.

Molecular mechanism for PS-facilitated Akt activation. Upon stimulation of a growth factor receptor, cytosolic Akt is recruited to the plasma membrane though interacting with PIP₃ and PS. The membrane interaction causes conformational changes of Akt, exposing T308 and S473 for phosphorylation by PDK1 and mTORC2, respectively. While S473 in the regulatory domain can be exposed by interacting with either PS or PIP₃, both lipids are required for the conformational change of the PH domain to expose T308 in the kinase domain for full activation of Akt. DHA, docosahexaenoic acid; PS, phsphatidylserine; PH, pleckstrin homology domain; RD, regulatory domain; KD, kinase domain. Adapted from reference [25].