1ε and p120-catenin control Ror2 function in noncanonical Wnt signaling
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 Frizzl...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:190746 |
| Acceso en línea: | https://ddd.uab.cat/record/190746 https://dx.doi.org/urn:doi:10.1002/1878-0261.12184 |
| Access Level: | acceso abierto |
| Palabra clave: | 1ε Noncanonical Wnt P120-catenin Ror2 |
| Sumario: | 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 1ε 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, 1ε 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 1ε by Fz-associated protein phosphatase 2A. Moreover, 1ε also regulates Ror2 protein levels; 1ε association stabilizes Ror2, which undergoes lysosomal-dependent degradation in the absence of this kinase. Although p120-catenin is not required for 1ε 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 1ε affects late responses to Wnt5a that are also sensitive to Ror2, such as 2 transcription, cell invasion, or cortical actin polarization. Our results explain how 1ε is activated by noncanonical Wnt and identify p120-catenin and 1ε as two critical factors controlling Ror2 function. |
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