ADP-ribosylation factors 1 and 6 regulate Wnt/β-catenin signaling via control of LRP6 phosphorylation

W. Kim, S. Y. Kim, T. Kim, M. Kim, D. J. Bae, H. I. Choi, In-San Kim, E. Jho

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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)P 2 (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.

Original languageEnglish
Pages (from-to)3390-3396
Number of pages7
JournalOncogene
Volume32
Issue number28
DOIs
Publication statusPublished - 2013 Jul 11
Externally publishedYes

Keywords

  • ADP-ribosylation factor (Arf)
  • LRP6
  • Phosphatidylinositol 4,5 bisphosphate (PtdIns (4,5)P )
  • Signal transduction
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Kim, W., Kim, S. Y., Kim, T., Kim, M., Bae, D. J., Choi, H. I., Kim, I-S., & Jho, E. (2013). ADP-ribosylation factors 1 and 6 regulate Wnt/β-catenin signaling via control of LRP6 phosphorylation. Oncogene, 32(28), 3390-3396. https://doi.org/10.1038/onc.2012.373