| First Author | Yamamoto H | Year | 2007 |
| Journal | Genes Cells | Volume | 12 |
| Issue | 11 | Pages | 1215-23 |
| PubMed ID | 17986005 | Mgi Jnum | J:135361 |
| Mgi Id | MGI:3793516 | Doi | 10.1111/j.1365-2443.2007.01128.x |
| Citation | Yamamoto H, et al. (2007) Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2. Genes Cells 12(11):1215-23 |
| abstractText | The receptor tyrosine kinase Ror2 plays important roles in mediating non-canonical Wnt5a signaling by activating the Wnt-JNK pathway and inhibiting the beta-catenin-TCF pathway. It has been shown that Ror2 is phosphorylated and activated by casein kinase Iepsilon when both molecules are over-expressed in cultured cells. However, it remains unknown whether or not Ror2 is phosphorylated upon Wnt5a stimulation. Here we show that Ror2 is phosphorylated on serine/threonine residues upon stimulation of cultured cells, expressing Ror2 endogenously, with Wnt5a, but not Wnt3a. It was found that treatment of cells with glycogen synthase kinase-3 (GSK-3) inhibitors (LiCl and SB216763) or small interfering RNAs (siRNAs) for GSK-3 (mainly GSK-3alpha) can inhibit Wnt5a-induced phosphorylation of Ror2. Immunoprecipitated Ror2 can also be phosphorylated by purified GSK-3alpha or GSK-3betain vitro, and ectopic co-expression of Ror2 and GSK-3 (mainly GSK-3alpha) in cultured cells results in Ror2 phosphorylation, irrespective of Wnt5a, that is sensitive to SB216763. These results indicate that GSK-3 is involved in Wnt5a-induced phosphorylation of Ror2. Moreover, it was found that Wnt5a-induced cell migration can be inhibited by SB216763 or by siRNA-mediated suppression of GSK-3alpha (and GSK-3beta) expression, further emphasizing the role(s) of GSK-3 in Wnt5a-induced signaling. |
