Dishevelled: The hub of Wnt signaling

Gao, Chan; Chen, Ye-Guang

doi:10.1016/j.cellsig.2009.11.021

Cited by 641 publications

(673 citation statements)

References 204 publications

Supporting

Mentioning

660

Contrasting

Unclassified

Order By: Relevance

“…Generally, it has been thought that Dvl proteins serve as a scaffold or hub proteins in the Wnt signalling pathways [1][2][3] . Daple binds to the PDZ domain, but not the DEP domain of Dvl that interacts with PKCλ and is essential to signal Rac activation.…”

Section: Discussionmentioning

confidence: 99%

“…D ishevelled (Dvl) is an essential scaffold protein that transduces both the canonical (β-catenin-dependent) and the non-canonical (β-catenin-independent) Wnt signalling pathways [1][2][3] . In the canonical Wnt signalling pathway, Wnt binding to a receptor complex composed of Frizzled (Fz) and low-density lipoprotein receptor-related protein 5/6 stabilises β-catenin via Dvl, leading to the activation of β-catenin-dependent transcription [4][5][6][7] .…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

et al. 2012

View full text Add to dashboard Cite

Dishevelled is the common mediator of canonical and non-canonical Wnt signalling pathways, which are important for embryonic development, tissue maintenance and cancer progression. In the non-canonical Wnt signalling pathway, the Rho family of small GTPases acting downstream of Dishevelled has essential roles in cell migration. The mechanisms by which the non-canonical Wnt signalling pathway regulates Rac activation remain unknown. Here we show that Daple (Dishevelled-associating protein with a high frequency of leucine residues) regulates Wnt5a-mediated activation of Rac and formation of lamellipodia through interaction with Dishevelled. Daple increases the association of Dishevelled with an isoform of atypical protein kinase C, consequently promoting Rac activation. Accordingly, Daple deficiency impairs migration of fibroblasts and epithelial cells during wound healing in vivo. These findings indicate that Daple interacts with Dishevelled to direct the Dishevelled/protein kinase λ protein complex to activate Rac, which in turn mediates the non-canonical Wnt signalling pathway required for cell migration.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

et al. 2012

View full text Add to dashboard Cite

show abstract

“…(2,3) Dishevelled (Dvl) protein relays Wnt canonical and noncanonical signals from receptors to downstream effectors. (4) In the canonical pathway, Dvl is recruited by the receptor frizzled and prevents the constitutive destruction of cytosolic b-catenin. In the noncanonical pathways, Dvl can signal through RhoA and Rac1 axis and other Wnt-related signals.…”

Section: Introductionmentioning

confidence: 99%

“…In the noncanonical pathways, Dvl can signal through RhoA and Rac1 axis and other Wnt-related signals. (4) These pathways have been reported to share components and crosstalk with other signaling networks, interactions that are cell type-dependent. (5) Previous studies in bone biology have demonstrated that Wnt/b-catenin signaling represents a major mechanism for the specification and development of mesenchymal precursors into osteoprogenitors and skeletal development.…”

Section: Introductionmentioning

confidence: 99%

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Caverzasio

Thouverey

2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Previous studies have shown that Wnt3a enhances the proliferation and inhibits the osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, we investigated the signaling pathways involved in Wnt3a-induced osteoblastic cell proliferation. Experiments with DKK1, a natural antagonist of Lrp5/6, indicated that Wnt/b-catenin did not play a major role in Wnt3a-induced osteoblastic cell proliferation. The use of selective inhibitors of known mitogenic pathways implicates Src family kinases (SFKs) and a protein kinase C (PKC) in this cellular response. Time-dependent analysis of signaling molecules activated by Wnt3a in MC3T3-E1 cells revealed parallel activation of the canonical pathway and of several tyrosine kinases, including SFKs and PDGF receptors (PDGF-Rs). Functional analysis with specific inhibitors suggested a major role of PDGF-Rs in mediating Wnt3a-induced cell proliferation. Further investigation with an si-RNA approach confirmed a predominant role of this receptor in this cellular response. The use of soluble decoy PDGF-Rs that can sequester extracellular PDGFs excluding that part of the increased PDGF receptor phosphorylation by Wnt3a was the result of autocrine production of PDGFs. A selective SFK inhibitor blunted the enhanced PDGF-R phosphorylation and cell proliferation induced by Wnt3a. Studies of initial events involved in the regulation of this pathway suggest a role of dishevelled. In conclusion, data presented in this study indicate that cell proliferation induced by Wnt3a in osteoblastic cells is mediated by a dishevelleddependent and b-catenin-independent pathway, which involves the transactivation of PDGF receptors. ß

show abstract

“…S2). We did not perform a KD of Dvl2, because doing so would inhibit the Wnt/b-catenin pathway [46] as well as the PCP pathway. Plasmids encoding a Dvl2-C-GFP or Dvl2DPDZ-GFP fusion protein were introduced into the lateral ventricle of P0-1 mice by electroporation.…”

Section: Blocking Pcp Signaling Alters the Distribution Of Npcs In Thmentioning

confidence: 99%

Roles of Planar Cell Polarity Signaling in Maturation of Neuronal Precursor Cells in the Postnatal Mouse Olfactory Bulb

et al. 2012

View full text Add to dashboard Cite

Neuronal precursor cells generated by stem cells in the subventricular zone (SVZ) migrate and differentiate into mature interneurons in the olfactory bulb (OB). The mechanisms responsible for the dynamic morphological changes in cells during this process are largely unknown. Wnt/planar cell polarity (PCP) signaling regulates various developmental events, including neuronal migration and neurite formation. Here, we studied the function of two components of the PCP pathway, Dishevelled2 and Van Gogh like-2, in the newborn neurons in the postnatal mouse OB. Electroporation-or lentivirus-mediated introduction of vectors carrying a knockdown or dominant-negative construct of these genes into the SVZ altered the distribution and dendrite formation of newborn neurons in the OB, suggesting that PCP signaling is involved in regulating the maturation of new neurons in the OB.

show abstract

Dishevelled: The hub of Wnt signaling

Cited by 641 publications

References 204 publications

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Roles of Planar Cell Polarity Signaling in Maturation of Neuronal Precursor Cells in the Postnatal Mouse Olfactory Bulb

Contact Info

Product

Resources

About