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Forkhead family transcription factor FKHRL1 is expressed in human megakaryocytes. Regulation of cell cycling as a downstream molecule of thrombopoietin signaling.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2001 May 04; Vol. 276 (18), pp. 15082-9. Date of Electronic Publication: 2001 Feb 13. - Publication Year :
- 2001
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Abstract
- FKHRL1, a member of the Forkhead transcription factor family, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt. This molecule is a mammalian homolog of DAF-16, which plays an important role in the longevity 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 line UT-7/TPO. Induced expression of active FKHRL1 led to cell cycle arrest at G0/G1 phase in this cell line. These results suggest that FKHRL1 plays an important role in the cell cycle of megakaryocytic cells as one of the downstream target molecules of phosphatidylinositol 3-kinase-Akt, presumably mediated through the activation or inactivation of cell cycle-associated gene(s).
- Subjects :
- Forkhead Box Protein O1
Forkhead Box Protein O3
Forkhead Transcription Factors
Humans
Phosphatidylinositol 3-Kinases metabolism
Phosphorylation
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-akt
Tumor Cells, Cultured
Cell Cycle
DNA-Binding Proteins metabolism
Megakaryocytes metabolism
Protein Serine-Threonine Kinases
Signal Transduction
Thrombopoietin metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 276
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11278373
- Full Text :
- https://doi.org/10.1074/jbc.M007958200