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

• Published in: EMBO reports Vol. 3; no. 1; pp. 63 - 68
• Main Authors: Staal, Frank J T, van Noort, Mascha, Strous, Ger J, Clevers, Hans C
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2002; Oxford University Press
• Subjects: Animals; beta Catenin; Calpain - antagonists & inhibitors; CHO Cells; Cricetinae; Cytoskeletal Proteins - physiology; DNA-Binding Proteins - physiology; Leupeptins - pharmacology; Lymphoid Enhancer-Binding Factor 1; Phosphorylation; Proto-Oncogene Proteins - physiology; Scientific Reports; Signal Transduction; Trans-Activators - physiology; Transcription Factors - physiology; Transcription, Genetic - physiology; Wnt Proteins; Zebrafish Proteins
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1093/embo-reports/kvf002

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.