APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway

被引:0
作者
王磊 [1 ,2 ]
陶一昕 [2 ]
张洁 [2 ]
王晓晴 [2 ]
周晌辉 [3 ]
贺林 [2 ]
马钢 [1 ,2 ,4 ]
机构
[1] Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
[2] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University
[3] Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
[4] Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University
基金
上海市自然科学基金; 中国国家自然科学基金; 国科技部“十一五”科技计划项目;
关键词
adenomatosis polyposis down-regulated 1 (APCDD1); Wnt signaling; receptor; Wnt5a; polarized cell migration;
D O I
暂无
中图分类号
R363 [病理生理学]; TN911.7 [信号处理];
学科分类号
0711 ; 080401 ; 080402 ; 100104 ;
摘要
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 Wnt5 a 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.
引用
收藏
页码:510 / 516
页数:7
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