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.
MRC Protein Phosphorylation Unit, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK.
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D048948:14-3-3 Proteins; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry / Q000378:metabolism
D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; D007328:Insulin; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt