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Wnt proteins synergize to activate ß-catenin signaling.
Alok, Anshula; Lei, Zhengdeng; Jagannathan, N Suhas; Kaur, Simran; Harmston, Nathan; Rozen, Steven G; Tucker-Kellogg, Lisa; Virshup, David M.
Afiliação
  • Alok A; Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857 Singapore.
  • Lei Z; Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857 Singapore.
  • Jagannathan NS; Centre for Computational Biology, Duke-NUS Medical School, 169857 Singapore.
  • Kaur S; Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857 Singapore.
  • Harmston N; Centre for Computational Biology, Duke-NUS Medical School, 169857 Singapore.
  • Rozen SG; Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857 Singapore.
  • Tucker-Kellogg L; Centre for Computational Biology, Duke-NUS Medical School, 169857 Singapore.
  • Virshup DM; Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857 Singapore.
J Cell Sci ; 130(9): 1532-1544, 2017 05 01.
Article em En | MEDLINE | ID: mdl-28289266
Wnt ligands are involved in diverse signaling pathways that are active during development, maintenance of tissue homeostasis and in various disease states. While signaling regulated by individual Wnts has been extensively studied, Wnts are rarely expressed alone, and the consequences of Wnt gene co-expression are not well understood. Here, we studied the effect of co-expression of Wnts on the ß-catenin signaling pathway. While some Wnts are deemed 'non-canonical' due to their limited ability to activate ß-catenin when expressed alone, unexpectedly, we find that multiple Wnt combinations can synergistically activate ß-catenin signaling in multiple cell types. WNT1- and WNT7B-mediated synergistic Wnt signaling requires FZD5, FZD8 and LRP6, as well as the WNT7B co-receptors GPR124 (also known as ADGRA2) and RECK. Unexpectedly, this synergistic signaling occurs downstream of ß-catenin stabilization, and is correlated with increased lysine acetylation of ß-catenin. Wnt synergy provides a general mechanism to confer increased combinatorial control over this important regulatory pathway.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Proteínas Wnt / Beta Catenina Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Proteínas Wnt / Beta Catenina Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article