Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction.
Signaling by the Wnt family of secreted proteins plays an important role in animal development and is often misregulated in carcinogenesis. Wnt signal transduction is controlled by the rate of degradation of beta-catenin by a complex of proteins including glycogen synthase kinase 3 (GSK3), adenomatous polyposis coli, and Axin. Dishevelled is required for Wnt signal transduction, and its activation results in stabilization of beta-catenin. However, the biochemical events underlying this process remain largely unclear. Here we show that Xenopus Dishevelled (Xdsh) interacts with a Xenopus Axin-related protein (XARP). This interaction depends on the presence of the Dishevelled-Axin (DIX) domains in both XARP and Xdsh. Moreover, the same domains are essential for signal transduction through Xdsh. Finally, our data point to a possible mechanism for signal transduction, in which Xdsh prevents beta-catenin degradation by displacing GSK3 from its complex with XARP.
Itoh
K
K
Department of Microbiology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Antipova
A
A
Ratcliffe
M J
MJ
Sokol
S
S
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D000072261:Dishevelled Proteins; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016415:Sequence Alignment; D015398:Signal Transduction; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D029961:Zebrafish Proteins
C111980:AXIN2 protein, Xenopus; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3