Forkhead family transcription factor FKHRL1 is expressed in human megakaryocytes - Regulation of cell cycling as a downstream molecule of thrombopoietin signaling

FKHRL1, a member of the Forkhead transcription factor family, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt. This molecule i s a mammalian homolog of DAF-16, which plays an important role in the longe vity of Caenorhabditis elegans. In this study we found that Akt and FKHRL1 proteins were detectable in highly purified normal human megakaryocytes and that these molecules were actually phosphorylated by thrombopoietin (TPO). To clarify the functional role of FKHRL1 in TPO signaling, we established a tetracycline-inducible system in the human TPO-dependent leukemia cell li ne UT-7/TPO. Induced expression of active FKHRL1 led to cell cycle arrest a t G(0)/G(1) phase in this cell line. These results suggest that FKHRL1 play s an important role in the cell cycle of megakaryocytic cells as one of the downstream target molecules of phosphatidylinositol 3-kinase-Akt, presumab ly mediated through the activation or inactivation of cell cycle-associated gene(s).