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J. Biol. Chem., Vol. 276, Issue 18, 15082-15089, May 4, 2001
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From the Departments of 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).
Forkhead Family Transcription Factor FKHRL1 Is Expressed in Human
Megakaryocytes
REGULATION OF CELL CYCLING AS A DOWNSTREAM MOLECULE OF
THROMBOPOIETIN SIGNALING*
,
,
§,
,
,
,
,
, and
**
Hematology,
§ Pediatrics, and ¶ Biochemistry, Jichi Medical School,
Tochigi, 329-0498 Japan and the
Department of Internal Medicine
II, Hokkaido University School of Medicine, Sapporo, Japan
*
This work was supported by grants-in-aid for cancer research
and scientific research from the Ministry of Education, Science and
Culture of Japan.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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