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J. Biol. Chem., Vol. 278, Issue 1, 537-544, January 3, 2003
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From the Graduate School of Biological Sciences, Nara Institute of
Science and Technology, Ikoma 630-0101, Japan
Fibroblast growth factor (FGF) signaling is
necessary for both proliferation and differentiation of lens cells.
However, the molecular mechanisms by which FGFs exert their
effects on the lens remain poorly understood. In this study, we show
that FGF-2 repressed the expression of lens-specific genes at the
proliferative phase in primary cultured lens cells. Using transfected
cells, we also found that the activity of L-Maf, a lens differentiation factor, is repressed by FGF/ERK signaling. L-Maf is shown to be phosphorylated by ERK, and introduction of mutations into the ERK
target sites on L-Maf promotes its stabilization. The stable L-Maf
mutant protein promotes the differentiation of lens cells from neural
retina cells. Taken together, these results indicate that FGF/ERK
signaling negatively regulates the function of L-Maf in
proliferative lens cells and that stabilization of the L-Maf protein is important for lens fiber differentiation.
The Stability of the Lens-specific Maf Protein is Regulated
by Fibroblast Growth Factor (FGF)/ERK Signaling in Lens Fiber
Differentiation*
,
*
This work was supported in part by the Foundation for Nara
Institute of Science and Technology.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: Gilmer Hall, Rm. 253, University of Virginia,
Charlottesville, VA 22903.
§
To whom correspondence should be addressed. Tel.: 81-743-72-5550;
Fax: 81-743-72-5559; E-mail: kyasuda@bs.aist-nara.ac.jp.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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