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Model of GSKIP-directed regulation of β-catenin and thus of Wnt signaling. GSKIP directly binds GSK3β and PKA. It controls the stability of β-catenin and thus its transcriptional activity through facilitating its phosphorylation (indicated by circled P) by the two kinases. GSK3β phosphorylates Ser-33/Ser-37/Thr-41 in the cytoplasm and targets it for proteasomal degradation. The phosphorylation of Ser-675 by PKA stabilizes β-catenin and enhances Wnt-induced signaling.
