Dickkopf Related Protein 4 (DKK4)

All DKKs have several potential sites for cleavage by furin-type proteases. Northern blot analysis detected no expression of DKK4, but RT-PCR analysis detected DKK4 expression in cerebellum, T-cell, esophagus, and lung cDNA libraries. Western blot analysis showed that DKK4 is secreted as 40-, 30- to 32-, and 15- to 17-kD proteins; these proteins were not significantly affected by N-glycanase treatment. N-terminal sequence analysis of the different forms suggested that DKK4 is proteolytically processed, possibly by intracellular furin-type proteases. Functional analysis determined that DKK4 blocks Xenopus Wnt8, Wnt3a, and Wnt2b, but not Dsh or Fz8, induction of a secondary axis in frog embryos, indicating that DKKs antagonize WNT function upstream of WNT receptors.