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Originally published In Press as doi:10.1074/jbc.M007958200 on February 13, 2001

J. Biol. Chem., Vol. 276, Issue 18, 15082-15089, May 4, 2001
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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*

Masaru TanakaDagger , Keita KiritoDagger , Yoshifumi KashiiDagger §, Mie UchidaDagger , Tomoko WatanabeDagger , Hitoshi Endo, Tomoyuki Endoh||, Ken-ichi Sawada||, Keiya OzawaDagger , and Norio KomatsuDagger **

From the Departments of Dagger  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

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).


* 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.

** To whom correspondence should be addressed: Dept. of Hematology, Jichi Medical School Minamikawachi-machi, Kawachi-gun, Tochigi-ken 329-0498, Japan. Tel.: 81-285-58-7353; Fax: 81-285-44-5258; E-mail: nkomatsu@ms.jichi.ac.jp.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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