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*

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.