Wnt Proteins Induce Dishevelled Phosphorylation via an LRP5/6- Independent Mechanism, Irrespective of Their Ability To Stabilize β-Catenin

• DOI: 10.1128/mcb.24.11.4757-4768.2004
• Publication Date: 2004-05-13T20:43:03Z
• Authors: José M. González-...; Keith R. Brennan; Leslie A. Castelo...; Anthony M. C. Brown
• Keywords: Dishevelled; LRP5; WNT5A; Beta-catenin; LRP6

Wnt glycoproteins play essential roles in the development of metazoan organisms. Many proteins, such as Wnt1, activate well-conserved canonical signaling pathway, which results accumulation β-catenin cytosol and nucleus. Other Wnts, Wnt5a, mechanisms do not involve are less well characterized. Dishevelled (Dvl) is a key component Wnt/β-catenin becomes phosphorylated upon activation this pathway. In addition to we show that several including trigger phosphorylation mammalian Dvl proteins occurs within 20 30 min. Unlike effects response Wnt5a concomitant with stabilization, indicating sufficient signaling. Moreover, neither Dickkopf1, inhibits by binding coreceptors LRP5 -6, nor dominant-negative LRP5/6 constructs could block Wnt-mediated phosphorylation. We conclude Wnt-induced independent receptors Wnts can elicit both LRP-dependent (to β-catenin) LRP-independent Dvl) signals. Our data also present general biochemical assay for protein function, those