Reactome | WNT mediated activation of DVL

WNT mediated activation of DVL

Stable Identifier

R-HSA-201688

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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The three human Dishevelled (DVL) proteins play a central and overlapping role in the transduction of the WNT signaling cascade (Lee et al, 2008; reviewed in Gao and Chen 2010). DVL activity is regulated by phosphorylation, although the details are not completely worked out. DVL likely exists as a phosphoprotein even in the absence of WNT stimulation, and is further phosphorylated upon ligand binding. Casein kinase 1epsilon (CSNK1E), casein kinase 2 (CSNK2) and PAR1 have all been reported to phosphorylate DVL (Willert et al, 1997; Sun et al, 2001; Cong et al, 2004; Ossipova et al, 2005). Upon pathway activation, phosphorylated DVL translocates to the plasma membrane through an interaction between the DVL PDZ domain and the FZD KTxxxW motif (Wong et al, 2003; Umbhauer et al, 2000; Kikuchi et al, 2011). At the plasma membrane, DVL is believed to oligomerize through its DIX domain, providing a platform for AXIN recruitment; recruitment of AXIN is also facilitated by interaction with LRP (Schwarz-Romond et al, 2007; Mao et al, 2001). DVL interacts with phosphatidylinositol-4-kinase type II (PI4KII) and phophatidylinositol-4-phosphate 5-kinase type I (PIP5KI) to promote formation of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the membrane, which is required for the clustering and phosphorylation of LRP6 and the recruitment of AXIN (Pan et al, 2008; Qin et al, 2009).

Literature References

PubMed ID	Title	Journal	Year
11336703	Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway Mao, J, Wang, J, Liu, B, Pan, W, Farr GH, 3rd, Flynn, C, Yuan, H, Takada, S, Kimelman, D, Li, L, Wu, D	Mol Cell	2001
22017973	New insights into the mechanism of Wnt signaling pathway activation Kikuchi, A, Yamamoto, H, Sato, A, Matsumoto, S	Int Rev Cell Mol Biol	2011
10990458	The C-terminal cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates Wnt/beta-catenin signalling Umbhauer, M, Djiane, A, Goisset, C, Penzo-Mendèz, A, Riou, JF, Boucaut, JC, Shi, DL	EMBO J.	2000
19561074	Regulation of phosphatidylinositol kinases and metabolism by Wnt3a and Dvl Qin, Y, Li, L, Pan, W, Wu, D	J. Biol. Chem.	2009
11433294	PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling Sun, TQ, Lu, B, Feng, JJ, Reinhard, C, Jan, YN, Fantl, WJ, Williams, LT	Nat. Cell Biol.	2001
18093802	Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, -2, and -3 Lee, YN, Gao, Y, Wang, HY	Cell. Signal.	2008
9214626	Casein kinase 2 associates with and phosphorylates dishevelled Willert, K, Brink, M, Wodarz, A, Varmus, H, Nusse, R	EMBO J.	1997
15935773	Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate development Ossipova, O, Dhawan, S, Sokol, S, Green, JB	Dev. Cell	2005
20006983	Dishevelled: The hub of Wnt signaling Gao, C, Chen, YG	Cell. Signal.	2010
17529994	The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization Schwarz-Romond, T, Fiedler, M, Shibata, N, Butler, PJ, Kikuchi, A, Higuchi, Y, Bienz, M	Nat. Struct. Mol. Biol.	2007
15459103	Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP Cong, F, Schweizer, L, Varmus, H	Development	2004
18772438	Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation Pan, W, Choi, SC, Wang, H, Qin, Y, Volpicelli-Daley, L, Swan, L, Lucast, L, Khoo, C, Zhang, X, Li, L, Abrams, CS, Sokol, SY, Wu, D	Science	2008
14636582	Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled Wong, HC, Bourdelas, A, Krauss, A, Lee, HJ, Shao, Y, Wu, D, Mlodzik, M, Shi, DL, Zheng, J	Mol Cell	2003