| First Author | Sun J | Year | 2011 |
| Journal | J Mol Biol | Volume | 405 |
| Issue | 2 | Pages | 519-30 |
| PubMed ID | 21075118 | Mgi Jnum | J:314560 |
| Mgi Id | MGI:6827205 | Doi | 10.1016/j.jmb.2010.11.010 |
| Citation | Sun J, et al. (2011) Biochemical and structural characterization of beta-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1. J Mol Biol 405(2):519-30 |
| abstractText | In the Wnt/beta-catenin signaling pathway, beta-catenin activates target genes through its interactions with the T-cell factor/lymphoid enhancer-binding factor (TCF/Lef) family of transcription factors. The crystal structures of complexes between the beta-catenin armadillo domain and the Lef-1 N-terminal domain show that the overall conformation and many of the interactions are similar to other published structures of TCFs bound to beta-catenin. However, a second salt bridge in other TCF-beta-catenin structures is absent in the structure of beta-catenin-Lef-1 complex, indicating that this feature is not obligatory for beta-catenin binding. Casein kinase II (CK2) has been shown to act as a positive regulator of Wnt signaling, and Lef-1 is a substrate of CK2. In vitro phosphorylation of purified Lef-1 was used to examine the effect of CK2 on the interaction of Lef-1 with beta-catenin. Mass spectrometry data show that CK2 phosphorylation of Lef-1 N-terminal domain results in a single phosphorylation site at Ser40. Isothermal titration calorimetry revealed that beta-catenin binds to nonphosphorylated or CK2-phosphorylated Lef-1 with the same affinity, which is consistent with the absence of phospho-Ser40 interactions in the crystal structure of phosphorylated Lef-1 N-terminal domain bound to beta-catenin. These data indicate that the effect of CK2 on the Wnt/beta-catenin pathway does not appear to be at the level of the Lef-1-beta-catenin interaction. |
