CK 1ε and p120‐catenin control Ror2 function in noncanonical Wnt signaling
| Autor: | Beatriz Del Valle-Pérez, Aida Villarroel, Mireia Duñach, Antonio García de Herreros, Meritxell Vinyoles, Guillem Fuertes, Raúl Peña, Josué Curto |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Delta Catenin Cancer Research Frizzled animal structures Ligands Receptor Tyrosine Kinase-like Orphan Receptors lcsh:RC254-282 Models Biological Mice p120‐catenin 03 medical and health sciences Downregulation and upregulation Genetics Animals Humans Phosphorylation Protein kinase A Wnt Signaling Pathway Research Articles Ror2 CK1ε Chemistry Wnt signaling pathway 1ε Catenins ROR2 General Medicine Protein phosphatase 2 p120-catenin lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Endocytosis Noncanonical wnt Cell biology body regions HEK293 Cells 030104 developmental biology Oncology embryonic structures Molecular Medicine Signal transduction Lysosomes Casein Kinases Protein Binding Research Article |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Molecular Oncology Molecular Oncology, Vol 12, Iss 5, Pp 611-629 (2018) |
| ISSN: | 1878-0261 1574-7891 |
| DOI: | 10.1002/1878-0261.12184 |
| Popis: | Canonical and noncanonical Wnt pathways share some common elements but differ in the responses they evoke. Similar to Wnt ligands acting through the canonical pathway, Wnts that activate the noncanonical signaling, such as Wnt5a, promote Disheveled (Dvl) phosphorylation and its binding to the Frizzled (Fz) Wnt receptor complex. The protein kinase CK1ε is required for Dvl/Fz association in both canonical and noncanonical signaling. Here we show that differently to its binding to canonical Wnt receptor complex, CK1ε does not require p120‐catenin for the association with the Wnt5a co‐receptor Ror2. Wnt5a promotes the formation of the Ror2–Fz complex and enables the activation of Ror2‐bound CK1ε by Fz‐associated protein phosphatase 2A. Moreover, CK1ε also regulates Ror2 protein levels; CK1ε association stabilizes Ror2, which undergoes lysosomal‐dependent degradation in the absence of this kinase. Although p120‐catenin is not required for CK1ε association with Ror2, it also participates in this signaling pathway as p120‐catenin binds and maintains Ror2 at the plasma membrane; in p120‐depleted cells, Ror2 is rapidly internalized through a clathrin‐dependent mechanism. Accordingly, downregulation of p120‐catenin or CK1ε affects late responses to Wnt5a that are also sensitive to Ror2, such as SIAH2 transcription, cell invasion, or cortical actin polarization. Our results explain how CK1ε is activated by noncanonical Wnt and identify p120‐catenin and CK1ε as two critical factors controlling Ror2 function This research was funded by grants from the Ministerio de Economía y Competitividad (MINECO) (BFU2015‐65153‐R co‐funded by Fondo Europeo de Desarrollo Regional‐FEDER‐UE) to MD, Agencia Estatal de Investigación (AEI) and FEDER (SAF2016‐76461‐R) to AGH and Fundació La Marató de TV3 (20120130) to MD and AGH. We also appreciate support from ICREA Academia, Generalitat de Catalunya (2014 SGR 32), and Instituto de Salud Carlos III (PIE15/00008). GF was recipient of a predoctoral fellowship from FPI |
| Databáze: | OpenAIRE |
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