| First Author | Takenaka K | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 353 |
| Issue | 2 | Pages | 501-8 |
| PubMed ID | 17182001 | Mgi Jnum | J:117258 |
| Mgi Id | MGI:3695869 | Doi | 10.1016/j.bbrc.2006.12.058 |
| Citation | Takenaka K, et al. (2007) GSK3beta positively regulates Hedgehog signaling through Sufu in mammalian cells. Biochem Biophys Res Commun 353(2):501-8 |
| abstractText | Hedgehog signaling plays important roles in embryonic patterning of multicellular organisms. This pathway is ultimately transmitted by the zinc-finger transcriptional factor Gli, of which activity is suppressed by Sufu, a negative regulator of this signaling. To clarify this regulation to more detail, we screened for Sufu-binding proteins. We identified GSK3beta as a specific binding partner of Sufu by mass spectrometric analysis. GSK3beta bound to Sufu both in vitro and in vivo. Down-regulation of GSK3beta expression by RNAi in Hedgehog-responsive cells attenuated Hedgehog signaling, suggesting that GSK3beta functions as a positive regulator of Hedgehog signaling. In addition, an in vitro kinase assay showed that GSK3beta phosphorylates Sufu and phosphorylation-mimicking mutant of Sufu showed significantly decreased ability to bind Gli1 and could not suppress the Gli-mediated expression of a reporter gene efficiently. These results strongly suggest that GSK3beta phosphorylates Sufu to positively regulate Hedgehog signaling in mammalian cells. |
