Identification of Two Smad4 Proteins in Xenopus
THEIR COMMON AND DISTINCT PROPERTIES*
- From the ‡Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502 and the§Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan
Abstract
Smad family proteins have been identified as mediators of intracellular signal transduction by the transforming growth factor-β (TGF-β) superfamily. Each member of the pathway-restricted, receptor-activated Smad family cooperates and synergizes with Smad4, called co-Smad, to transduce the signals. Only Smad4 has been shown able to function as a common partner of the various pathway-restricted Smads in mammals. Here we have identified a novel Smad4-like molecule in Xenopus (XSmad4β) as well as a Xenopus homolog of a well established Smad4 (XSmad4α). XSmad4β is 70% identical to XSmad4α in amino acid sequence. Both of the Xenopus Smad4s can cooperate with Smad1 and Smad2, the pathway-restricted Smads specific for bone morphogenetic protein and TGF-β, respectively. However, they show distinct properties in terms of their developmental expression patterns, subcellular localizations, and phosphorylation states. Moreover, XSmad4β, but not XSmad4α, has the potent ability to induce ventralization when microinjected into the dorsal marginal region of the 4-cell stage of the embryos. These results suggest that the two XenopusSmad4s have overlapping but distinct functions.
Footnotes
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↵* This work was supported by grants from the Ministry of Education, Science and Culture of Japan (to E. N.).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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AB022721 and AB022722.
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↵¶ To whom correspondence should be addressed. Fax: 81-75-753-4235; E-mail: L50174{at}sakura.kudpc.kyoto-u.ac.jp.
- Abbreviations:
- TGF-β
-
transforming growth factor-β
- BMP
-
bone morphogenetic protein
- HA
-
hemagglutinin
- RT-PCR
-
reverse transcription-coupled polymerase chain reaction
- XSmad
-
Xenopus Smad
- hSmad
-
human Smad
- MH1
-
mad homology 1 (amino-terminal domain)
- DAI
-
dorsoanterior index
- MH2
-
mad homology 2 (carboxyl-terminal domain)
- DPC
-
deleted in pancreatic cancer
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- Received December 16, 1998.
- Revision received January 28, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
