FIGURE 1.

Phosphylation of domain 3 OH of PIP2 by the regulatory component leads to the formation of PIP3 upon modulation by EGFR. PIP3 then recruits proteins with pleckstrin homology motifs (PH) to the cell membrane, specifically Akt and phosphoinositide-dependent protein kinase 1 (PDK1), causing PDK1 and Mammalian Target of Rapamycin Complex 2 to phosphorylate AKT. AKT is triggered and consequently, mTORC1 is activated, which in turn stimulates P70S6 kinase and inactivates eukaryotic translation inhibitory factor 4E-binding protein 1, inducing cellular survival, cellular proliferation, and protein biosynthesis. The tumor suppressor genes PTEN modulate the intracellular concentration of PIP3 by converting it to PIP2 via its lipid phosphatase ability, thus preventing the initiation of Akt and its cascade networks.