Characterization of Mouse Dishevelled (Dvl) Proteins in Wnt/Wingless Signaling Pathway

Lee, Jong-Seo; Ishimoto, Akinori; Yanagawa, Shin-ichi

doi:10.1074/jbc.274.30.21464

Cited by 136 publications

(129 citation statements)

References 41 publications

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“…5C). These findings indicated that the changes in Dvl isoforms were attributable to Wnt-dependent phosphorylation, consistent with observations previously made in other cells (39,40). Interestingly, these mobility shifts have been reported to correlate with noncanonical Wnt signaling (41).…”

Section: Dvl-2 and Dvl-3 Are Phosphorylated In Response Tosupporting

confidence: 80%

Wnt-3a-dependent Cell Motility Involves RhoA Activation and Is Specifically Regulated by Dishevelled-2*[boxs]

Endo

Wolf

Muraiso

et al. 2005

Journal of Biological Chemistry

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Wnts stimulate cell migration, although the mechanisms responsible for this effect are not fully understood. To investigate the pathways that mediate Wnt-dependent cell motility, we treated Chinese hamster ovary cells with Wnt-3a-conditioned medium and monitored changes in cell shape and movement. Wnt-3a induced cell spreading, formation of protrusive structures, reorganization of stress fibers and migration. Although Wnt-3a stabilized ␤-catenin, two inhibitors of the ␤-catenin/canonical pathway, Dickkopf-1 and a dominant-negative T cell factor construct, did not reduce motility. The small GTPase RhoA also was activated by Wnt-3a. In contrast to ␤-catenin signaling, inhibition of Rho kinase partially blocked motility. Because Dishevelled (Dvl) proteins are effectors of both canonical and noncanonical Wnt signaling, we used immunofluorescent analysis and small interference RNA technology to evaluate the role of Dvl in cell motility. Specific knock-down of Dvl-2 expression markedly reduced Wnt-3a-dependent changes in cell shape and movement, suggesting that this Dvl isoform had a predominant role in mediating Wnt-3a-dependent motility in Chinese hamster ovary cells.

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Section: Dvl-2 and Dvl-3 Are Phosphorylated In Response Tosupporting

confidence: 80%

Wnt-3a-dependent Cell Motility Involves RhoA Activation and Is Specifically Regulated by Dishevelled-2*[boxs]

Endo

Wolf

Muraiso

et al. 2005

Journal of Biological Chemistry

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“…Further research is necessary to analyze the presented possibilities. The APP-PS1 mice treated with rosiglitazone did not show increased levels of Dvl-3, but showed increased levels of b-catenin and the inhibited form of GSK-3b, and as Dvl-3 is activated right after the binding of Wnt to the receptor, 61,62 this result may help to reveal a part of the mechanism of the cross talk. 63 Our results indicate that APP-PS1 mice treated with lithium and rosiglitazone had a significantly lower area occupied by plaques than did transgenic control mice.…”

Section: Discussionmentioning

confidence: 96%

Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1ΔE9 mouse model of Alzheimer's disease

2009

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“…However, axin is not the only protein involved in modulating GSK3b activity through protein-protein interactions, and therefore these other proteins, in concert with axin, likely play an essential role in regulating GSK3b-mediated tau phosphorylation. For example, overexpression of Dvl is sufficient to decrease tau phosphorylation by GSK3b at several sites (Lee et al 1999;Mudher et al 2001). This inhibition is not due to a direct effect of Dvl on GSK3b, as Dvl and GSK3b do not interact (Li et al 1999), and therefore other interacting proteins must be involved.…”

Section: Discussionmentioning

confidence: 99%

Axin negatively affects tau phosphorylation by glycogen synthase kinase 3β

Stoothoff¹,

Bailey²,

Mi³

et al. 2002

Journal of Neurochemistry

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Glycogen synthase kinase 3b (GSK3b) is an essential protein kinase that regulates numerous functions within the cell. One critically important substrate of GSK3b is the microtubuleassociated protein tau. Phosphorylation of tau by GSK3b decreases tau-microtubule interactions. In addition to phosphorylating tau, GSK3b is a downstream regulator of the wnt signaling pathway, which maintains the levels of b-catenin. Axin plays a central role in regulating b-catenin levels by bringing together GSK3b and b-catenin and facilitating the phosphorylation of b-catenin, targeting it for ubiquitination and degradation by the proteasome. Although axin clearly facilitates the phosphorylation of b-catenin, its effects on the phosphorylation of other GSK3b substrates are unclear.Therefore in this study the effects of axin on GSK3b-mediated tau phosphorylation were examined. The results clearly demonstrate that axin is a negative regulator of tau phosphorylation by GSK3b. This negative regulation of GSK3b-mediated tau phosphorylation is due to the fact that axin efficiently binds GSK3b but not tau and thus sequesters GSK3b away from tau, as an axin mutant that does not bind GSK3b did not inhibit tau phosphorylation by GSK3b. This is the first demonstration that axin negatively affects the phosphorylation of a GSK3b substrate, and provides a novel mechanism by which tau phosphorylation and function can be regulated within the cell.

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Characterization of Mouse Dishevelled (Dvl) Proteins in Wnt/Wingless Signaling Pathway

Cited by 136 publications

References 41 publications

Wnt-3a-dependent Cell Motility Involves RhoA Activation and Is Specifically Regulated by Dishevelled-2*[boxs]

Wnt-3a-dependent Cell Motility Involves RhoA Activation and Is Specifically Regulated by Dishevelled-2*[boxs]

Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1ΔE9 mouse model of Alzheimer's disease

Axin negatively affects tau phosphorylation by glycogen synthase kinase 3β

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