Figure 3.

The phosphatidylinositol-3-kinase (PI3) pathway. PI3K is activated by binding of the regulatory subunit p85 to activated tyrosine kinase receptors or G-protein-coupled receptors. The catalytic subunit p110 generates phosphatidylinositol-3,4,5-triphosphate (PIP3) by phosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) in the membrane, which in turn functions as a second messenger through interaction with pleckstrin homology domain–containing proteins such as phosphoinositide-dependent kinase (PDK). Activation of PDK results in the dual phosphorylation of protein kinase B (PKB/Akt). Akt phosphorylates multiple substrates resulting in the regulation of several processes such as cell survival, proliferation, or cell metabolism. Through the modification of mechanistic target of rapamycin (mTOR) signaling, PI3K further modulates cellular functions such as protein synthesis and cell growth.