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Vol. 11, Issue 2, 555-565, February 2000
and
*Department of Biochemistry, The Cancer Institute of Japanese
Foundation for Cancer Research, and Research for the Future Program,
Japan Society for Promotion of Science, Tokyo 170-8455, Japan; and
Bone morphogenetic proteins (BMPs) are pleiotropic growth and
differentiation factors belonging to the transforming growth factor-Department of Ophthalmology, Hiroshima University School
of Medicine, Hiroshima 734-8551, Japan
(TGF-) superfamily. Signals of the TGF--like ligands are
propagated to the nucleus through specific interaction of transmembrane
serine/threonine kinase receptors and Smad proteins. GCCGnCGC has been
suggested as a consensus binding sequence for Drosophila
Mad regulated by a BMP-like ligand, Decapentaplegic. Smad1 is one of
the mammalian Smads activated by BMPs. Here we show that Smad1 binds to
this motif upon BMP stimulation in the presence of the common Smad,
Smad4. The binding affinity is likely to be relatively low, because
Smad1 binds to three copies of the motif weakly, but more repeats of
the motif significantly enhance the binding. Heterologous reporter
genes (GCCG-Lux) with multiple repeats of the motif respond to BMP
stimulation but not to TGF- or activin. Mutational analyses reveal
several bases critical for the responsiveness. A natural BMP-responsive
reporter, pTlx-Lux, is activated by BMP receptors in P19 cells but not
in mink lung cells. In contrast, GCCG-Lux responds to BMP stimulation
in both cells, suggesting that it is a universal reporter that directly detects Smad phosphorylation by BMP receptors.
Corresponding author. E-mail address:
mkawabat-ind{at}umin.u-tokyo.ac.jp.
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