| First Author | Bryja V | Year | 2007 |
| Journal | J Cell Sci | Volume | 120 |
| Issue | Pt 4 | Pages | 586-95 |
| PubMed ID | 17244647 | Mgi Jnum | J:120773 |
| Mgi Id | MGI:3707948 | Doi | 10.1242/jcs.03368 |
| Citation | Bryja V, et al. (2007) Wnt-5a induces Dishevelled phosphorylation and dopaminergic differentiation via a CK1-dependent mechanism. J Cell Sci 120(Pt 4):586-95 |
| abstractText | Previously, we have shown that Wnt-5a strongly regulates dopaminergic neuron differentiation by inducing phosphorylation of Dishevelled (Dvl). Here, we identify additional components of the Wnt-5a-Dvl pathway in dopaminergic cells. Using in vitro gain-of-function and loss-of-function approaches, we reveal that casein kinase 1 (CK1) delta and CK1epsilon are crucial for Dvl phosphorylation by non-canonical Wnts. We show that in response to Wnt-5a, CK1epsilon binds Dvl and is subsequently phosphorylated. Moreover, in response to Wnt-5a or CK1epsilon, the distribution of Dvl changed from punctate to an even appearance within the cytoplasm. The opposite effect was induced by a CK1epsilon kinase-dead mutant or by CK1 inhibitors. As expected, Wnt-5a blocked the Wnt-3a-induced activation of beta-catenin. However, both Wnt-3a and Wnt-5a activated Dvl2 by a CK1-dependent mechanism in a cooperative manner. Finally, we show that CK1 kinase activity is necessary for Wnt-5a-induced differentiation of primary dopaminergic precursors. Thus, our data identify CK1 as a component of Wnt-5a-induced signalling machinery that regulates dopaminergic differentiation, and suggest that CK1delta/epsilon-mediated phosphorylation of Dvl is a common step in both canonical and non-canonical Wnt signalling. |
