Abstract:Cells take advantage of cross‐talk in signaling pathways to integrate diverse signals and produce coordinated responses. In this issue of EMBO Reports, Jeong et al discover that the Wnt co‐receptor, low‐density lipoprotein (LDL) receptor‐related protein LRP6, negatively regulates Hippo signaling by serving as a binding sink to sequester and inhibit Merlin, an activator of Hippo signaling (Jeong et al, 2020). This regulation is nutrient‐responsive, likely using LRP6 O‐GlcNAcylation as a molecular switch.
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