AKT/PKB kinase is a key signaling component of one of the most frequently activated pathways in cancer and is a major target of cancer drug development. The present study uncovered that growth factors binding to RTKs lead to activation of a non-receptor tyrosine kinase, Ack1 (TNK2), which directly phosphorylates AKT at a conserved tyrosine 176 residue. Tyr176-phosphorylated AKT binds to phosphatidic acid and localizes to the plasma membrane, leading to AKT activation. Expression levels of Tyr176-phosphorylated-AKT and Tyr284-phosphorylated-Ack1 were positively correlated with the severity of disease progression, and inversely correlated with the survival of breast, prostate, lung and pancreatic cancer patients.
