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J. Biol. Chem., Vol. 276, Issue 42, 38441-38448, October 19, 2001
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From the Department of Genetics, B-3, Osaka University Medical
School, and Core Research for Evolutional Science and Technology, Japan
Science and Technology Corporation, 2-2 Yamadaoka, Suita,
Osaka 565-0871, Japan
The Drosophila segment polarity gene
fused encodes a putative protein-serine/threonine kinase,
and plays a critical role in the signal transduction for Hedgehog
(Hh)-dependent gene expression. We show that the
Drosophila Schneider 2 (S2) cell line has the potential to
transduce the Hh-triggered intracellular signals, leading to the
activation of target gene expression, when a transcription factor,
Cubitus interruptus (Ci), is provided exogenously. Using S2 cells
transfected with the Ci-expressing plasmid and a patched promoter reporter construct, we demonstrate that the forced expression of Fused (Fu) stimulates Hh-triggered and Ci-dependent
transcriptional activation. The N-terminal kinase domain of Fu is
required for this activity, but the C-terminal domain is not. Two
kinase-inactive Fu mutants fail to enhance the reporter activation,
indicating that the kinase catalytic activity is essential for this
function. Negative components of the Hh-signaling pathway, Costal-2 and Suppressor of Fused, strongly antagonize the Fu activity, irrespective of the presence or absence of the Fu C-terminal domain, suggesting an
indirect mechanism for the inhibition of Fu by these proteins. Furthermore, mutational analyses of threonine 158 and serine 159, in
the activation segment of the Fu protein kinase, indicate that threonine 158 is essential for Fu activity and that phosphorylation of
this threonine residue may be involved in the activation of the
kinase catalytic activity upon Hh stimulation.
The Fused Protein Kinase Regulates Hedgehog-stimulated
Transcriptional Activation in Drosophila Schneider 2 Cells*
,
*
This work was supported in part by grants-in-aid from the
Ministry of Education, Science, Sports and Technology 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.
Supported by a research fellowship from the Japan Society for the
Promotion of Science.
§
To whom correspondence should be addressed.
Tel.: 81-6-6879-3318; Fax: 81-6-6879-3319; E-mail:
fukunaga@genetic.med.osaka-u.ac.jp.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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