AKT signaling is regulated via phosphorylation at T308 and S473 through PDK1 and mTORC2, respectively. In specific, AkT is phosphorylated at T308 within its catalytic domain and at S473 within its C-terminal regulatory domain, resulting in the complete activation of Akt kinase. The PI3K/Akt pathway is also crucial for regulation of Akt signaling. It is negatively modulated by PTEN, which is a lipid phosphatase dephosphorylation PI (3,4,5) P3 in the D3 position of the inositol ring. PI3K is activated in response to growth factors such as insulin receptors binding to their respective ligands. PI3K forms PIP3 from PIP2 in the plasma membrane.