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Survival factors such as NGF activate receptor protein-tyrosine kinases, leading to activation of PI 3-kinase and formation of PIP3. PIP3 recruits the protein kinase Akt to the plasma membrane where it is activated as a result of phosphorylation by PDK. Akt then appears to phosphorylate a number of proteins that contribute to cell survival. The targets of Akt that have been implicated in suppression of apoptosis include the Bcl-2 family member Bad, caspase-9, several transcription factors, and the protein kinase GSK-3, which affects cell metabolism and protein synthesis.
