Dishevelled proteins are important intermediates of Wnt signaling pathways. Dsh inhibits glycogen synthase kinase-3β promoting β-catenin stabilization. Dsh proteins also participate in the planar cell polarity pathway by acting through JNK. There are three Dsh homologs, Dvl1, Dvl2 and Dvl3 in mammals. Upon treatment with Wnt proteins, Dvls become hyperphosphorylated and accumulate in the nucleus. Dvl proteins also associate with actin fibers and cytoplasmic vesicular membranes and mediate endocytosis of the Fzd receptor after Wnt protein stimulation. Overexpression of Dvl has been reported in certain cancers.
[1] Logan, C.Y. and Nusse, R. (2004) Annu. Rev. Cell Dev. Biol. 20, 781-810.
[2] Boutros, M. and Mlodzik, M. (1999) Mech. Dev. 83, 27-37.
[3] Lee, J.S. et al. (1999) J. Biol. Chem. 274, 21464-70.
[4] Itoh, K. et al. (2005) J. Biol. 4, 3.1-3.12.
[5] Capelluto, D.G. et al. (2002) Nature 419, 726-729.
[6] Chen, W. et al. (2003) Science 301, 1391-1394.
[7] Okino , K. et al. (2003) Oncol. Rep. 10, 1219-1223.
[8] Uematsu, K. et al. (2003) Oncogene 22, 7218-7221.