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, Eisuke Nishida

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)

Abstract

Recent studies have shown that Drosophila Dishevelled (Dsh), an essential component of the wingless signal transduction, is also involved in planar polarity signaling through the c-Jun N-terminal kinase (JNK)/stress- activated protein kinase (SAPK) pathway in Drosophila. 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 in Xenopus 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.

Original languageEnglish
Pages (from-to)30957-30962
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number43
DOIs
Publication statusPublished - Oct 22 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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