Intracellular Signaling by Β‐catenin

Fagotto, François; Glück, Ursula; Funayama, Noriko; Gumbiner, Barry M.

doi:10.1016/s0248-4900(97)86842-6

Cited by 4 publications

(5 citation statements)

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“…In contrast to our observation in C. elegans that cortical b-catenin inhibits Wnt signaling, it has been reported, in Xenopus and Drosophila, that overexpression of a membrane-tethered form of b-catenin activates Wnt signaling (Miller and Moon, 1997;Cox et al, 1999;Wieschaus, 2001, 2004;Cong et al, 2003). Nevertheless, it has also been reported that overexpression of cadherin, which likely recruits b-catenin to the cortex, inhibits Wnt signaling (Fagotto et al, 1996;Gottardi et al, 2001). Such effects on Wnt signaling are explained by the sequestration of Wnt-signaling components: Axin or APC by membranetethered b-catenin in the former experiments (Tolwinski and Wieschaus, 2001;Cong et al, 2003), and b-catenin itself by the overexpression of cadherin in the latter experiments (Graham et al, 2000;Huber and Weis, 2001).…”

Section: Cortical B-catenin and Apc In Other Organismscontrasting

confidence: 92%

Cortical β-Catenin and APC Regulate Asymmetric Nuclear β-Catenin Localization during Asymmetric Cell Division in C. elegans

2007

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In C. elegans, Wnt signaling regulates a number of asymmetric cell divisions. During telophase, WRM-1/beta-catenin localizes asymmetrically to the anterior cortex and the posterior daughter's nucleus. However, cortical WRM-1's functions are not known. Here, we use a membrane-targeted form of WRM-1 to show that cortical WRM-1 inhibits Wnt signaling and the nuclear localization of WRM-1. These functions are mediated by APR-1/APC, which regulates WRM-1 nuclear export. We also show that APR-1 as well as PRY-1/Axin and Dishevelled homologs localize asymmetrically to the cortex. Our results suggest a model in which cortical WRM-1 recruits APR-1 to the anterior cortex before and during division, and the cortical APR-1 stimulates WRM-1 export from the anterior nucleus at telophase. Because beta-catenin and APC are localized to the cortex in many cell types in different species, our results suggest that these cortical proteins may regulate asymmetric divisions or Wnt signaling in other organisms as well.

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Section: Cortical B-catenin and Apc In Other Organismscontrasting

confidence: 92%

Cortical β-Catenin and APC Regulate Asymmetric Nuclear β-Catenin Localization during Asymmetric Cell Division in C. elegans

2007

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“…An increase in the expression of the junctional partners of b-catenin (for example cadherin and a-catenin) results in a signi®cantly reduced b-catenin signaling (Fagotto et al, 1996;Sanson et al, 1996;Simcha et al, 1998;Sadot et al, 1998). Moreover, changes in the level of plakoglobin were also shown to in¯uence this balance in b-catenin's availability, by a ecting b-catenin's stability in the cell (Miller and Moon, 1997;Salomon et al, 1997;Simcha et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to this structural role in cell adhesion, bcatenin and its Drosophila homolog, armadillo, are key components of the wg/wnt-signaling pathway (Peifer and Wieschaus, 1990;Peifer et al, 1993;Wodarz and Nusse, 1998) that regulates developmental processes, including speci®cation of the anterior-posterior segment polarity in Drosophila (Peifer et al, 1993), and axis determination in developing Xenopus embryos (Heasman et al, 1994). Signaling by b-catenin is carried out mainly by the nuclear pool of the protein, and recruitment of this protein to adherens junctions, by overexpressing cadherins inhibits its signaling activity (Fagotto et al, 1996;Sanson et al, 1996;Simcha et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Differential interaction of plakoglobin and β-catenin with the ubiquitin-proteasome system

et al. 2000

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b-Catenin and plakoglobin are closely related armadillo family proteins with shared and distinct properties; Both are associated with cadherins in actin-containing adherens junctions. Plakoglobin is also found in desmosomes where it anchors intermediate ®laments to the desmosomal plaques. b-Catenin, on the other hand, is a component of the Wnt signaling pathway, which is involved in embryonic morphogenesis and tumorigenesis. A key step in the regulation of this pathway involves modulation of b-catenin stability. A multiprotein complex, regulated by Wnt, directs the phosphorylation of bcatenin and its degradation by the ubiquitin-proteasome system. Plakoglobin can also associate with members of this complex, but inhibition of proteasomal degradation has little e ect on its levels while dramatically increasing the levels of b-catenin. b-TrCP, an F-box protein of the SCF E3 ubiquitin ligase complex, was recently shown to play a role in the turnover of b-catenin. To elucidate the basis for the apparent di erences in the turnover of bcatenin and plakoglobin we compared the handling of these two proteins by the ubiquitin-proteasome system. We show here that a deletion mutant of b-TrCP, lacking the F-box, can stabilize the endogenous b-catenin leading to its nuclear translocation and induction of b-catenin/ LEF-1-directed transcription, without a ecting the levels of plakoglobin. However, when plakoglobin was overexpressed, it readily associated with b-TrCP, e ciently competed with b-catenin for binding to b-TrCP and became polyubiquitinated. Fractionation studies revealed that about 85% of plakoglobin in 293 cells, is Triton X-100-insoluble compared to 50% of b-catenin. These results suggest that while both plakoglobin and b-catenin can comparably interact with b-TrCP and the ubiquitination system, the sequestration of plakoglobin by the membrane-cytoskeleton system renders it inaccessible to the proteolytic machinery and stabilizes it.

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“…Cadherinmediated signaling may act to regulate the availability cAMP levels. In principle, this could occur through negative regulation of adenylyl cyclase by a Gi family protein of free ␤-catenin (Fagotto et al, 1996), and therefore feed into the same signaling pathway as the Wnt recep-activated by a G protein-coupled receptor such as Smoothened, but this effect is more likely to be indirect tor. ␤-catenin is a v-Src PTK substrate and its phosphorylation perturbs cadherin function in v-Src-transformed and involve the Fused protein kinase (Therond et al, 1996).…”

Section: Cadherins and Cateninsmentioning

confidence: 99%