Adenomatosis polyposis down-regulated 1 (APCDD1) is a transmembrane glycoprotein that negatively
regulates Wnt/β-catenin canonical signaling by binding with Wnt ligands and receptors. We analyzed the role
of APCDD1 in the Wnt5a/c-Jun non-canonical signaling pathway and demonstrated that APCDD1 can interact
in vitro with Wnt5a, a classical ligand, and Ror2, a receptor of non-canonical Wnt signaling. Furthermore, we
verified the binding of APCDD1 and Ror2 in primary cells of mouse skin. Moreover, APCDD1 seems to form
a complex with Ror2 and Vangl2 in the cell, and complex formation can be improved by adding Wnt5a. In
the presence of Wnt5a and Ror2, APCDD1 can induce the phosphorylation of c-Jun, a transcription factor of
Wnt5a non-canonical signaling, and its phosphorylation level is a readout of Wnt5a signaling. Wound-healing
assay shows that APCDD1 accelerates polarized cell migration during Wnt5a-induced wound closure. Therefore,
it is very likely that APCDD1 regulates Wnt5a/c-Jun non-canonical signaling as co-receptor binding with both
Wnt5a and Ror2.
WANG Lei (王磊), TAO Yixin (陶一昕), ZHANG Jie (张洁), WANG Xiaoqing (王晓晴), ZHOU Shanghui (周晌辉), HE Lin (贺林), MA Gang *(马钢)
. APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway[J]. Journal of Shanghai Jiaotong University(Science), 2019
, 24(4)
: 510
-516
.
DOI: 10.1007/s12204-019-2083-5
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