Wnt signals are transmitted through N-terminally dephosphorylated β-catenin

Frank J.T. Staal, Mascha van Noort, Ger J. Strous, Hans C. Clevers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

291 Citaten (Scopus)

Samenvatting

β-catenin mediates Wnt signaling by acting as the essential co-activator for TCF transcription factors. Wnt signaling increases the half-life and therefore the absolute level of β-catenin in responding cells. The current model states that these changes in β-catenin stability set the threshold for Wnt signaling. However, we find that pharmacological inhibition of proteasome activity by ALLN leads to accumulation of cytosolic β-catenin but not to increased TCF-mediated transcription. In addition, in temperature-sensitive ubiquitylation mutant CHO cells inhibition of ubiquitylation increases β-catenin levels, but does not induce transcriptional activation of TCF reporter genes. Using an antibody specific for β-catenin dephosphorylated at residues Ser37 and Thr41, we show that Wnt signals specifically increase the levels of dephosphorylated β-catenin, whereas ALLN does not. We conclude that changes in the phosphorylation status of the N-terminus of β-catenin that occur upon Wnt signaling independently affect the signaling properties and half-life of β-catenin. Hence, Wnt signals are transduced via N-terminally dephosphorylated β-catenin.

Originele taal-2Engels
Pagina's (van-tot)63-68
Aantal pagina's6
TijdschriftEMBO Reports
Volume3
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 2002
Extern gepubliceerdJa

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