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Fig. 1. Dishevelled mediates at least three signaling cascades. (A) The canonical WNT pathway. WNT signals are received by a Frizzled (FZ) receptor and a LRP co-receptor. The signal is transduced through Dishevelled and various other proteins, leading eventually to the stabilization of ß-Catenin, which then together with LEF/TCF controls the transcription of target genes. (B) The non-canonical or planar cell polarity (PCP) cascade. A signal is received by a FZ receptor (in Drosophila, no WNT has yet been implicated in PCP signaling in vertebrates, although WNT11 and WNT5a are necessary), and transduced via Dishevelled to RAC and RHO, which then activate downstream targets to modulate the actin cytoskeleton. (C) The WNT/Ca²⁺ pathway. WNT signaling through the FZ receptors and Dishevelled and G-proteins leads to the release of intracellular calcium and signaling via Phospholipase C, CamK2 and PKC (Miller et al., 1999a; Sheldahl et al., 1999; Sheldahl et al., 2003). Image reproduced with permission from BioMedCentral (see Habas and Dawid, 2005). APC, Adenomatous Polyposis Coli; CKI, Casein kinase 1; CamK2, calcium/calmodulin-dependent kinase 2; GBP, GSK3 Binding Protein; GSK3, Glycogen synthase kinase 3; JNK, Jun kinase; LRP, Low-density lipoprotein receptor-related protein; PKC, Protein kinase C; TCF/LEF, Lymphoid Enhancer-Binding Factor/T-Cell Specific Transcription Factor; ß-TrCP, Beta-Transducin Repeat Containing Protein; ROCK, RHO-associated coiled-coil forming kinase.

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