A Mechanism for Wnt Coreceptor Activation

摘要: LDL receptor related proteins 5 and 6 (LRP5/6) their Drosophila homolog Arrow are single-span transmembrane essential for Wnt/beta-catenin signaling, likely via acting as Wnt coreceptors. How activates LRP5/6/Arrow to initiate signal transduction is not well defined. Here we show that a PPPSP motif, which reiterated five times in the intracellular domain, necessary sufficient trigger signaling. A single upon transfer receptor, fully pathway, inducing complete axis duplication Xenopus TCF/beta-catenin-responsive transcription human cells. We further signal-ing stimulates, requires, phosphorylation of creates an inducible docking site Axin, scaffolding protein controlling beta-catenin stability. Our study identifies critical signaling module key phosphorylation-dependent activation step complex reveals unifying logic by Wnts, growth factors, cytokines.