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 journalArticle

114 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

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this