ADP-ribosylation factors 1 and 6 regulate Wnt/β-catenin signaling via control of LRP6 phosphorylation
Copyright policy )ADP-ribosylation factors 1 and 6 regulate Wnt/β-catenin signaling via control of LRP6 phosphorylation
It has been shown that inhibition of GTPase-activating protein of ADP-ribosylation factor (Arf), ArfGAP, with a small molecule (QS11) results in synergistic activation of Wnt/β-catenin signaling. However, the role of Arf in Wnt/β-catenin signaling has not yet been elucidated. Here, we show that activation of Arf is essential for Wnt/β-catenin signaling. The level of the active form of Arf (Arf-GTP) transiently increased in the presence of Wnt, and this induction event was abrogated by blocking the interaction between Wnt and Frizzled (Fzd). In addition, knockdown of Fzds, Dvls or LRP6 blocked the Wnt-mediated activation of Arf. Consistently, depletion of Arf led to inhibition of Wnt-mediated membrane PtdIns (4,5)P2 (phosphatidylinositol 4, 5-bisphosphate) synthesis and LRP6 phosphorylation. Overall, our data suggest that transient activation of Arf modulates LRP6 phosphorylation for the transduction of Wnt/β-catenin signaling.
- Seoul National University Korea (Republic of)
- Korean Association Of Science and Technology Studies Korea (Republic of)
- University of Seoul Korea (Republic of)
- Kyungpook National University Korea (Republic of)
- Korea Institute of Science and Technology Korea (Republic of)
Phosphatidylinositol 4,5-Diphosphate, Time Factors, ADP-Ribosylation Factors, Frizzled Receptors, Mice, HEK293 Cells, ADP-Ribosylation Factor 6, Gene Knockdown Techniques, Low Density Lipoprotein Receptor-Related Protein-6, Wnt3A Protein, Animals, Humans, ADP-Ribosylation Factor 1, Phosphorylation, beta Catenin, Signal Transduction
Phosphatidylinositol 4,5-Diphosphate, Time Factors, ADP-Ribosylation Factors, Frizzled Receptors, Mice, HEK293 Cells, ADP-Ribosylation Factor 6, Gene Knockdown Techniques, Low Density Lipoprotein Receptor-Related Protein-6, Wnt3A Protein, Animals, Humans, ADP-Ribosylation Factor 1, Phosphorylation, beta Catenin, Signal Transduction
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