From Extracellular Signals to Intracellular Responses

PI3K–AKT signaling is frequently initiated when an extracellular molecule binds to a cell-surface receptor. Growth factors and hormones, for example, can activate receptor tyrosine kinases or other upstream receptors, triggering a sequence of molecular interactions that leads to PI3K activation.

Once activated, PI3K modifies membrane phosphoinositides by converting phosphatidylinositol-4,5-bisphosphate (PIP2) into phosphatidylinositol-3,4,5-trisphosphate (PIP3). This change in the composition of the plasma membrane creates a signaling platform that facilitates the recruitment of proteins containing pleckstrin homology domains.

Among these proteins is AKT, also known as protein kinase B. Recruitment of AKT to the membrane allows its subsequent phosphorylation and activation. Activated AKT can then regulate a broad range of downstream targets, translating the original extracellular signal into coordinated cellular responses.