Fig. 3. Schematic diagram of various Arrow/Lrp5/Lrp6 mutant proteins and their signaling properties. The wild-type Lrp5/Lrp6 is depicted on the left. Black bars in the intracellular domain represent PPPSP motifs. Lrp6C (without most of the intracellular domain), Lrp5N (secreted extracellular domain) and Lrp6m5 (alanine substitution of the S/T residue in all five PPP[S/T]P motifs) are dominant-negative reagents that can block canonical Wnt signaling. The following receptor mutants are constitutively active, i.e. they can activate ß-catenin signaling in the absence of Wnt: (1) Arrow/Lrp5/Lrp6N (without the extracellular domain but anchored on the membrane); (2) myristoylated Lrp5C (intracellular domain anchored to the plasma membrane via a form of lipid modification); (3) a single PPPSP motif linked to a truncated LDLR; and (4) Dfz2-Arr[intra], which is a fusion of the Arrow intracellular domain with the Dfz2 carboxyl-terminal tail. The Lrp5/Lrp6 intracellular domain that is not anchored to the plasma membrane is inactive. For reasons unclear at the moment, the Arrow intracellular domain designed to anchor to the plasma membrane via myristoylation is inactive in fly embryos, although its protein expression has not been examined (Tolwinski et al., 2003).