Figure 8.

Synergistic regulation of Wnt signaling by Dkk and Krm family proteins: Diversity of potential functional complexes formed. A–C, possible schematic models for the interaction of Dkk, Krm, and LRP5/6 proteins on the cell surface, illustrating the potential for a wide spectrum of functional complexes to form to provide exquisite fine-tuning of Wnt-signaling activity. The diversity of potential complexes includes both high affinity Dkk–LRP5/6 inhibitory interactions mediated by the CRD2 domain of Dkk proteins and relatively low-affinity interactions involving the conserved NXI(R/K) motif located in the flexible N terminus of Dkks. The potential complexes shown highlight the tendency of the Krm ECD to form stable dimers.