TY - JOUR
T1 - ADP-ribosylation factors 1 and 6 regulate Wnt/β-catenin signaling via control of LRP6 phosphorylation
AU - Kim, W.
AU - Kim, S. Y.
AU - Kim, T.
AU - Kim, M.
AU - Bae, D. J.
AU - Choi, H. I.
AU - Kim, I. S.
AU - Jho, E.
N1 - Funding Information:
This work was supported by grants from the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2006-2004046 and 2012R1A2A2A01012472 to E-HJ; 2010-0029206 to I-SK; 2011-0003980 to S-YK). WK, TK, and MK were supported by the Brain Korea 21 program.
PY - 2013/7/11
Y1 - 2013/7/11
N2 - 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.
AB - 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.
KW - ADP-ribosylation factor (Arf)
KW - LRP6
KW - Phosphatidylinositol 4,5 bisphosphate (PtdIns (4,5)P)
KW - Signal transduction
KW - Wnt
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UR - http://www.scopus.com/inward/citedby.url?scp=84880281030&partnerID=8YFLogxK
U2 - 10.1038/onc.2012.373
DO - 10.1038/onc.2012.373
M3 - Article
C2 - 22907437
AN - SCOPUS:84880281030
VL - 32
SP - 3390
EP - 3396
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 28
ER -
