Wnt3a-stimulated LRP6 phosphorylation is dependent upon arginine methylation of G3BP2

Abstract

Wnt signaling is initiated upon binding of Wnts to Frizzleds and their co-receptors LRP5/6. The signal is then propagated to several downstream effectors, mediated by the phosphoprotein scaffold, Dishevelled. We report a novel role for arginine methylation in regulating Wnt3a-stimulated LRP6 phosphorylation. G3BP2, a Dishevelled-associated protein, is methylated in response to Wnt3a. The Wnt3a-induced LRP6 phosphorylation is attenuated by G3BP2 knock-down, chemical inhibition of methyl transferase activity, or expression of methylation-deficient mutants of G3BP2. Arginine methylation of G3BP2 appears to be a Wnt3a-sensitive “switch” regulating LRP6 phosphorylation and canonical Wnt/β-catenin signaling.