FIG. 9.
Model for cell cycle regulation by the PI3K/PKB/Forkhead pathway. When cells do not receive growth factors in early G1, PKB is not activated and Forkheads (FH) remain active. This results in upregulation of the genes for p27kip1 and p130 along with yet unidentified target genes, leading to cell cycle exit in nonhematopoietic cells and, with the additional regulation of the Bim and FasL gene products, to apoptosis in hematopoietic cells. Subsequent activation of PKB through receptor tyrosine kinases (RTK) leads to phosphorylation of FH (indicated by the circled p) and inactivation of Forkheads by nuclear exclusion and therefore to cell cycle reentry via downregulation of the Forkhead cell cycle-regulatory target genes. See the text for further details.