Jun 10, 2008 · Through experiments in egg extract and reconstitution with purified proteins, we identify a mechanism whereby LRP6 stabilizes β-catenin independently of Axin degradation by directly inhibiting GSK3's phosphorylation of β-catenin.

Notably, the low-density lipoprotein receptor-related protein 6 (LRP6), an indispensable co-receptor for WNT, is frequently overexpressed in colorectal, liver, breast and pancreatic adenocarcinomas in association with increased WNT/β -catenin signaling.

In this scenario, LRP6 via its five phosphorylated PPPSPxS motifs can engage Axin and inhibit GSK3 simultaneously, a possibility that is also conceivable if LRP6 aggregates in trans in signalosomes.

Jan 5, 2024 · Overexpression of LRP6 further potentiated Axin1 degradation mediated by RSPO1 or CK1ε. In addition, recombinant RSPO1 and Wnt3A proteins synergistically downregulated the protein expression of Axin1 and enhanced the transcriptional activity of …

We also show that axin, a key scaffolding protein in the Wnt pathway, is required for Lrp6 phosphorylation via its ability to recruit Gsk3, and inhibition of Gsk3 at the plasma membrane blocks Wnt/β-catenin signaling.

Jun 15, 2007 · We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and β-catenin stabilization.

May 5, 2013 · Inactivation of Axin diminished its association with β-catenin and LRP6, thereby inhibiting β-catenin phosphorylation and enabling activated LRP6 to selectively recruit active Axin for inactivation reiteratively. Our findings reveal mechanisms for scaffold regulation and morphogen signaling.

Jun 6, 2008 · To correlate LRP6 signaling activity with Axin binding, we performed Axin co-immunoprecipitation experiments with LRP6 single mutant receptors using the WT LRP6 and LRP6 m5 as positive and negative controls, respectively.

Lrp6 phosphorylation is crucial to beta-catenin stabilization and pathway activation by promoting Axin and Gsk3 recruitment to phosphorylated sites. Here, we summarize how proline-directed kinases (Gsk3, PKA, Pftk1, Grk5/6) and non-proline-directed kinases (CK1 family) act upon Lrp6, how the phosphorylation is regulated by ligand binding and ...

We also show that axin, a key scaffolding protein in the Wnt pathway, is required for Lrp6 phosphorylation via its ability to recruit Gsk3, and inhibition of Gsk3 at the plasma membrane blocks Wnt/beta-catenin signaling.