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Wnt signals are transmitted through N‐terminally dephosphorylated β‐catenin
Author(s) -
Staal Frank J T,
van Noort Mascha,
Strous Ger J,
Clevers Hans C
Publication year - 2002
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvf002
Subject(s) - wnt signaling pathway , beta catenin , phosphorylation , microbiology and biotechnology , ubiquitin , catenin , proteasome , signal transduction , biology , transcription factor , mutant , chemistry , gene , biochemistry
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.