Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6 |
| |
Authors: | Wolf Joshua Palmby Todd R Gavard Julie Williams Bart O Gutkind J Silvio |
| |
Institution: | Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA. |
| |
Abstract: | Binding of Wnt to Frizzled, and either of two members of the low-density-lipoprotein receptor-related protein family, LRP5/6, leads to beta-catenin activation by a poorly understood mechanism. LRP5/6 exhibit five highly conserved PPPS/TP motifs in their intracellular region, among which the first PPPS/TP site is rapidly phosphorylated upon Wnt stimulation. By the use of full-length LRP6 mutants harboring multiple mutations involving the five PPPS/TP motifs, we found that this first PPPS/TP phosphoacceptor site is alone not sufficient or strictly necessary for beta-catenin activation. Instead, we show that each LRP6 PPPS/TP motif contributes in a combinatorial fashion to activate the canonical Wnt-beta-catenin pathway. |
| |
Keywords: | Wnt LRP6 β-Catenin Nuclear signaling Cancer |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|