Phosphorylation of Dishevelled by Protein Kinase RIPK4 Regulates Wnt Signaling
| Autor: | Kim Newton, Sarah G. Hymowitz, XiaoDong Huang, Anthony Wynshaw-Boris, Michael Kakunda, Christine Yu, Paul Polakis, Victoria Pham, Jo Anne Hongo, Jennie R. Lill, Bob Y. Liu, Rami N. Hannoush, Richard M. Harland, James C. McGann, Jinfeng Liu, Vishva M. Dixit |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Beta-catenin
Transplantation Heterologous Dishevelled Proteins Protein Serine-Threonine Kinases Xenopus Proteins Biology Article Cell Line Xenopus laevis Cytosol Cell Line Tumor Neoplasms Wnt3A Protein Animals Humans Phosphorylation Protein kinase A Wnt Signaling Pathway beta Catenin Protein kinase C Adaptor Proteins Signal Transducing Ovarian Neoplasms chemistry.chemical_classification Multidisciplinary Wnt signaling pathway LRP6 LRP5 Phosphoproteins Molecular biology Dishevelled HEK293 Cells chemistry Gene Knockdown Techniques Low Density Lipoprotein Receptor-Related Protein-6 biology.protein Female Neoplasm Transplantation |
| Zdroj: | Science. 339:1441-1445 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | Receptor interacting protein kinase 4 (RIPK4) is required for epidermal differentiation (1–4) and is mutated in Bartsocas-Papas syndrome (5, 6). While RIPK4 binds protein kinase C (5, 6), RIPK4 signaling mechanisms are largely unknown. We show that ectopic RIPK4 induces cytosolic β-catenin accumulation and a transcriptional program similar to Wnt3a, whereas kinase-defective or Bartsocas-Papas syndrome RIPK4 mutants do not. Ectopic ripk4 synergized with Wnt family member xwnt8 in Xenopus, whereas ripk4 morpholinos or kinase-defective RIPK4 antagonized Wnt signaling. Mechanistically, RIKP4 interacted constitutively with the Wnt adaptor protein DVL2 and, after Wnt3a stimulation, with the co-receptor LRP6. Phosphorylation of DVL2 at Ser298 and Ser480 by RIPK4 favored canonical Wnt signaling. Growth of a Wnt-dependent N-Tera2 xenograft tumor model was suppressed by RIPK4 knockdown, suggesting that RIPK4 overexpression may contribute to the growth of certain tumor types. |
| Databáze: | OpenAIRE |
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