Dishevelled: at the crossroads of divergent intracellular signaling pathways.
During the development of multicellular organisms the formation of complex patterns relies on specific cell-cell signaling events. For tissues to become spatially organized and cells to become committed to specialized fates it is absolutely crucial for proper development that the underlying signaling systems receive and route information correctly. Recently, a wealth of genetic and biochemical experimental data has been collected about prevalent evolutionary conserved signaling families, such as the Wnts, Dpp/BMPs, and Hedgehogs, in flies, worms, and vertebrates. Paradoxically, members of a particular signaling family often have receptors with similar biochemical binding properties, though they activate different intracellular pathways in vivo and can be phenotypically distinguished. How are their specific biological responses then generated? With respect to signaling specificity in Wnt pathways, Dishevelled is an intriguing protein; in Drosophila melanogaster it is required in two distinct signaling pathways, that share Frizzled receptors of similar structure, but have distinct intracellular signaling routes. Recent results suggest that Dishevelled is a multifunctional protein at the crossroads of divergent Wnt/Fz pathways. Dishevelled appears to be a key factor in Wnt signaling to read' signals coming from the plasma membrane and route them into the correct intracellular pathways.
Boutros
M
M
Developmental Biology, Programme, European Molecular Biology Laboratory, Meyerhofstrasse 169117, Heidelberg, Germany.
Mlodzik
M
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051153:Wnt Proteins; D051155:Wnt1 Protein; D014981:Xenopus / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008565:Membrane Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; C000606588:dsh protein, Drosophila; C058784:fz protein, Drosophila; C074622:wg protein, Drosophila