PI 3-kinase, Akt and cell survival.

Phosphoinositide 3-OH kinase (PI 3-kinase) provides cells with a survival signal that allows them to withstand apoptotic stimuli. Many tumour cells display elevated levels of PI 3-kinase products as a result of deletion of the phosphatase PTEN, activation of Ras or expression of autocrine growth factors. As a result they are relatively resistant to apoptosis. The mechanisms for PI 3-kinase survival signalling are becoming clear. The principal mediator is Akt, a PI 3-kinase activated protein kinase. Akt has direct effects on the apoptosis machinery, for example targeting the pro-apoptotic Bcl-2 related protein, BAD. It also affects the transcriptional response to apoptotic stimuli, for example by acting on Forkhead factors and also influence the activity of the p53 family. In addition, novel connections between the metabolic effects of Akt and its control of survival have recently been made.