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J. Biol. Chem., Vol. 278, Issue 16, 14066-14073, April 18, 2003
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From the We demonstrate that Dvl-1, casein kinase I
Casein Kinase I
Enhances the Binding of Dvl-1 to Frat-1
and Is Essential for Wnt-3a-induced Accumulation of
-Catenin*
,
¶
Department of Biochemistry, Graduate School
of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi,
Minami-ku, Hiroshima 734-8551, Japan and the § Sorst Project
and Department of Life Science (Biology), University of Tokyo, 3-8-1, Komaba, Meguro-ku, Tokyo 153-8902, Japan
(CKI
), and Frat-1 activate the Wnt signaling pathway cooperatively.
The amino acid region 228-250 of Dvl-1 was necessary for its binding
to Frat-1, and the interaction of Dvl-1 with Frat-1 was enhanced by
CKI
. Coexpression of Dvl-1 and Frat-1 caused accumulation of
-catenin synergistically in L cells. Both proteins also activated the transcriptional activity of T-cell factor-4 (Tcf-4) synergistically in human embryonic kidney 293 cells, but coexpression of
Dvl-1-(
228-250), which lacks the amino acid region 228-250 from
Dvl-1, and Frat-1 did not. Dvl-1, but not Dvl-1-(
228-250), acted
synergistically with CKI
to activate Tcf-4. Depletion of CKI
by
double-stranded RNA interference in HeLa S3 cells led to the inhibition
of Wnt-3a-induced phosphorylation of Dvl and the binding of Dvl-1 to
Frat-1. Furthermore, depletion of CKI
reduced the Wnt-3a-induced
accumulation of
-catenin, although it did not affect the basal level
of
-catenin. These results indicate that
CKI
-dependent phosphorylation of Dvl enhances the
formation of a complex of Dvl-1 with Frat-1 and that this complex leads
to the activation of the Wnt signaling pathway.
*
This work was supported by Grants-in-Aid for Scientific
Research and for Scientific Research on priority areas from the
Ministry of Education, Science, and Culture, Japan (2001, 2002).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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