Effect of multiple phosphorylation events on the transcription factors FKHR, FKHRL1 and AFX.

The insulin-stimulated phosphoinositide 3-kinase (PI 3-kinase)/3-phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (PKB) kinase cascade is believed to play a critical role in metabolic control and cell survival, largely mediated through PKB phosphorylation of many proteins. Recent findings demonstrate that the transcription factors FKHR (forkhead in rhabdomyosarcoma), AFX (ALL1 fused gene from chromosome X) and FKHRL1 (FKHR-like 1; termed FKHR isoforms) are phosphorylated by PKB in cells, leading to their exit from the nucleus. These exciting results suggest that FKHR isoforms may be critical effectors of PI 3-kinase/PDK1/PKB signalling in vivo.