Fig. 8.
Schematic model of the involvement of LRP6 in Gαs-coupled receptor signaling. (A) We propose that LRP6 binds to the inactive Gαsβγ heterotrimer on the plasma membrane in the absence of GPCR ligands. (B) Ligands induce the aggregation of LRP6 and cause the accumulation of Gαsβγ on the plasma member to set up a functional GPCR-Gαs-AC complex for cAMP generation and PKA activation. Activated PKA, in turn, phosphorylates LRP6 and accelerates the binding of G protein complexes to LRP6 to enable enhanced production of cAMP.