Identification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signalling.

Identification of a DNA aptamer that inhibits sclerostin’s antagonistic effect on Wnt signaling

The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6

The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases s...

Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism

Cells often respond to diverse environmental stresses by inducing stress granules (SGs) as an adaptive mechanism. SGs are generally assembled as a result of aggregation of mRNAs stalled in a translational pre-initiation complex, mediated by a set of RNA-binding proteins such as G3BP and TIA-1. SGs may serve as triage centres for storage, translation re-initiation or degradation of specific mRNA...

Wnt signalling: Antagonistic Dickkopfs

Dickkopf proteins are secreted antagonists of the Wnt cell signalling molecules, which have a novel mode of action. Dickkopf1 binds to the LRP5/6 Wnt co-receptor and prevents the formation of active Wnt--Frizzled--LRP5/6 receptor complexes, thus blocking the canonical Wnt--beta-catenin pathway.

Off-track takes Frizzled off the canonical path.

Like many other signalling pathways, the Wnt pathway is seen as part of a network that integrates extracellular information mediated by a variety of cell surface proteins to produce cell context-specific outputs. The identification of Frizzled as Wnt receptors (Bhanot et al, 1996) provided the essential link between extracellular Wnts and the intracellular components of Wnt signal transduction....