Reactome | ppDVL recruits RAC

ppDVL recruits RAC

Stable Identifier

R-HSA-3858475

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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WNT-dependent activation of dishevelled proteins (DVL) induces the activation of RAC and the formation of a RAC:DVL complex in HEK293 cells (Habas et al, 2003). Activation of RAC and stimulation of PCP/CE signaling depends on the DEP but not the DIX domain of DVL (Axelrod et al, 1998; Boutros et al, 1998, Habas et al, 2001, Habas et al, 2003). There are conflicting reports regarding the requirement for the DVL PDZ domain in the WNT-dependent activation of RAC (Habas et al, 2003; Cajanek et al, 2013). Activation of RAC almost certainly involves a RAC-specific GEF activity, potentially associated with DVL. In dopaminergic neurons, TIAM1 has been identified as the GEF for WNT5A- and DVL-dependent activation of RAC (Cajanek et al, 2013), however it is not clear whether this is generally true in other cell types and for other WNT ligands. In some cases, RAC activation correlates with activation of the downstream effector c-Jun N terminal kinase (JNK). This is thought to regulate reorganization of the cytoskeleton but the mechanism of JNK activation is unknown. In other cases, JNK activation appears to be dispensable to the WNT response (Yamanaka et al, 2002; Habas et al, 2003; Rosso et al, 2005; reviewed in Heaseman and Ridley, 2008; Lai et al, 2009).

Literature References

PubMed ID	Title	Journal	Year
19365405	Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis Lai, SL, Chien, AJ, Moon, RT	Cell Res.	2009
11779461	Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1 Habas, R, Kato, Y, He, X	Cell	2001
18719708	Mammalian Rho GTPases: new insights into their functions from in vivo studies Heasman, SJ, Ridley, AJ	Nat. Rev. Mol. Cell Biol.	2008
11751577	JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates Yamanaka, H, Moriguchi, T, Masuyama, N, Kusakabe, M, Hanafusa, H, Takada, R, Takada, S, Nishida, E	EMBO Rep.	2002
23109420	Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons Cajánek, L, Ganji, RS, Henriques-Oliveira, C, Theofilopoulos, S, Konik, P, Bryja, V, Arenas, E	Mol. Cell. Biol.	2013
9674432	Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling Boutros, M, Paricio, N, Strutt, DI, Mlodzik, M	Cell	1998
9716412	Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways Axelrod, JD, Miller, JR, Shulman, JM, Moon, RT, Perrimon, N	Genes Dev	1998
12533515	Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation Habas, R, Dawid, IB, He, X	Genes Dev	2003
15608632	Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development Rosso, SB, Sussman, D, Wynshaw-Boris, A, Salinas, PC	Nat. Neurosci.	2005