Distinct Domains of Mouse Dishevelled Are Responsible for the c-Jun N-terminal Kinase/Stress-activated Protein Kinase Activation and the Axis Formation in Vertebrates*
- Tetsuo Moriguchi‡,
- Kaoru Kawachi‡,
- Sachiko Kamakura‡,
- Norihisa Masuyama‡,
- Hiroaki Yamanaka‡,
- Kunihiro Matsumoto§,
- Akira Kikuchi¶ and
- Eisuke Nishida‡‖
- From the ‡Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, the§Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, and the ¶Department of Biochemistry, Hiroshima University School of Medicine, Minami-ku, Hiroshima 734-8551, Japan
Abstract
Recent studies have shown thatDrosophila Dishevelled (Dsh), an essential component of thewingless signal transduction, is also involved in planar polarity signaling through the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway inDrosophila. Here, we show that expression of a mouse homolog of Dsh (mDvl-1) in NIH3T3 cells activates JNK/SAPK, and its activator MKK7. A C-terminal half of mDvl-1 which contains the DEP domain was sufficient for the activation of JNK/SAPK, whereas an N-terminal half of mDvl-1 as well as the DEP domain is required for stimulation of the TCF/LEF-1-dependent transcriptional activation, a β-catenin-dependent process. A single amino acid substitution (Met for Lys) within the DEP domain (mDvl-1 (KM)) abolished the JNK/SAPK-activating activity of mDvl-1, but did not affect the activity to activate the LEF-1-dependent transcription. Ectopic expression of mDvl-1 (KM) or an N-terminal half of mDvl-1, but not the C-terminal, was able to induce secondary axis inXenopus embryos. Because the secondary axis formation is dependent on the Wnt/β-catenin signaling pathway, these results suggest that distinct domains of mDvl-1 are responsible for the two downstream signaling pathways, the β-catenin pathway and the JNK/SAPK pathway in vertebrates.
Footnotes
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↵* This work was supported by grants from the Ministry of Education, Science and Culture 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.
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↵‖ To whom correspondence should be addressed. Fax: 81-75-753-4235; E-mail: L50174@sakura.kudpc.kyoto-u.ac.jp.
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↵2 Kamakura, S., Moriguchi, T., and Nishida, E. (1999) J. Biol. Chem. 274, 26563–26571
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↵3 N. Masuyama, and E. Nishida, unpublished data.
- Abbreviations:
- JNK
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c-Jun N-terminal kinase
- SAPK
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stress-activated protein kinase
- MAPK
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mitogen-activated protein kinase
- MAPKK
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MAPK kinase
- HA
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hemagglutinin
- MBP
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myelin basic protein
- GST
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glutathioneS-transferase
- Wg
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Wingless
- Dsh
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Dishevelled
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- Received December 30, 1998.
- Revision received June 11, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
