DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation

摘要: DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis including head induction, skeletal development, limb patterning. also implicated osteoporosis, arthritis, cancer represents potential therapeutic target for the treatment of these diseases. high affinity antagonistic ligand LRP6, which coreceptor acts together with Frizzled serpentine receptor to initiate signal transduction. Two different models have been proposed account mechanism by LRP6 function. One model suggests binding disrupts Wnt-induced Frizzled-LRP6 complex formation, whereas other proposes interaction promotes internalization degradation, thereby reducing cell surface level. To clarify molecular basis action, we examined how affects endogenous several mammalian lines mouse embryonic fibroblasts. Here show inhibits but induces neither down-regulation from nor reduction total level has no effect on rate continuous half-life (about 4.7 h) LRP6. We conclude inhibition independent degradation.