FIGURE 9.
Model of Wnt-5a/DARPP-32-mediated inhibition of breast cancer cell migration. Autocrine or paracrine acting Wnt-5a ligand activates Frizzled-3 receptors that via Gαs stimulates cAMP formation by adenylyl cyclases (AC). cAMP activates PKA, which phosphorylates DARPP-32 at Thr-34 and CREB at Ser-133. pThr34-DARPP-32 suppresses filopodia formation in part by reducing CDC42 activity. In addition, pThr34-DARPP-32 inhibits PP1, which in turn leads to enhanced CREB phosphorylation. CREB mediates transcription of genes that also regulate cell migration by an as yet unidentified mechanism.