Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells.
Dishevelled (Dsh/Dvl) proteins are known to mediate Wnt signaling by up-regulating beta-catenin levels and stimulating T cell factor (TCF)/LEF-1-dependent transcription. We have identified a new Dvl-mediated signaling pathway in that mouse Dvl proteins, when expressed in COS-7 cells, stimulate c-Jun-dependent transcription activity and the kinase activity of the c-Jun N-terminal kinase (JNK). The DEP domain of Dvl1 is essential for JNK activation. By contrast, all three conserved domains of Dvl, including DIX, PDZ, and DEP, are required for up-regulation of beta-catenin and for stimulation of LEF-1-mediated transcription in mammalian cells. Thus, Dvl can lead to two different signaling pathways. Furthermore, the small G proteins of Cdc42 or Rac1, which are involved in JNK activation by many stimuli, do not appear to play a major role in Dvl-mediated JNK activation, because the dominant negative mutants of Cdc42 and Rac1 could not inhibit Dvl-induced JNK activation. This suggests that Dvl may activate JNK via novel pathways.
Li
L
L
Department of Pharmacology and Physiology and Department of Oncology, University of Rochester, Rochester, New York 14642-8711, USA.
Yuan
H
H
Xie
W
W
Mao
J
J
Caruso
A M
AM
McMahon
A
A
Sussman
D J
DJ
Wu
D
D
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D010750:Phosphoproteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495267:CTNNB1 protein, mouse; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases