FIGURE 8.

Model for role of WDFY2 in endosomal control of Akt2 signaling. In this model the initial event in Akt2 activation is the interaction of its PH domain with phosphatidylinositol 3,4,5-trisphosphate (PIP3) generated at the plasma membrane. Subsequently, the kinase interacts with APPL in the initial phase of endocytosis, when the levels of phosphatidylinositol 3,4,5-trisphosphate decrease. Phosphatidylinositol 3-phosphate (PI3P) is then generated, and WDFY2 replaces APPL on endosomes. Akt2 binds to WDFY2 and becomes stabilized and protected from degradation. Substrate phosphorylation can proceed from WDFY2-enriched endosomes.