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J. Biol. Chem., Vol. 277, Issue 27, 24638-24647, July 5, 2002
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From the The Hedgehog (Hh) signaling molecule is required
for the development of numerous tissues in Drosophila.
Within the cell, Hh signal transduction utilizes a large protein
complex consisting of the Fused (Fu), Costal2 (Cos2), and Cubitis
interruptus (Ci) proteins, but the functional interactions between
these proteins are still largely uncharacterized. Using a baculovirus
system, we demonstrate that the serine/threonine kinase Fu
phosphorylates the kinesin-like protein Cos2 when coexpressed with
Cos2. Coexpression of Cos2 and a kinase-inactive version of Fu
eliminates the majority of Cos2 phosphorylation. We then show that the
primary Fu-induced phosphorylation site of Cos2 is serine 572, whereas
serine 931 is phosphorylated to a lesser extent. Mutation of serine 572 to alanine eliminates most, but not all, specific phosphopeptides of
Cos2 when coexpressed with Fu. We also demonstrate that the phosphorylation pattern of Cos2 produced by baculovirus coexpression with kinase-dead Fu is almost identical to the phosphorylation pattern
of Cos2 isolated from unstimulated S2 cells. Finally, the
phosphorylation pattern of Cos2 produced by baculovirus coinfection with wild-type Fu is almost identical to that of Cos2 isolated from S2
cells stimulated by Hh, indicating that phosphorylation of serines 572 and 931 is a genuine Hh signaling event. This study clarifies the
unique functions of Fu and Cos2 in Hh signal transduction and
identifies only the second known phosphorylation site of a kinesin-like molecule.
Hedgehog-stimulated Phosphorylation of the Kinesin-related
Protein Costal2 Is Mediated by the Serine/Threonine Kinase Fused*
§¶,
**,, and
Hooper Foundation, Department of
Microbiology and Immunology, University of California, San Francisco,
California 94143 and the Howard Hughes Medical Institute and
Department of Medicine, University of California,
San Francisco, California 94143
*
This work was supported by NCI, National Institutes of
Health, Grant CA44338 (to J. M. B.).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.
Present address: Dept. of Molecular Genetics, University of
Cincinnati, Cincinnati, OH 45267-0524.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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