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Dickkopf-related protein 1 (DKK-1) is a member of the Dickkopf family and is a secreted protein that inhibits the canonical WNT pathway by competitive binding to low-density lipoprotein receptors (LRP)-5 and 6 with high affinity, thereby decreasing β-catenin protein stability (Niehrs). DKK-1 regulates embryonic development and contains two conserved cysteine-rich domains separated by a linker region and an N-terminal signal peptide (Krupnik et al.; Lieven et al.). A family of human DKK-related genes composed of DKK-1, DKK-2, DKK-3, and DKK-4 have been characterized together with a unique DKK-3 related protein termed Soggy (Krupnik et al.). DKK-1 has been shown to support the generation of myeloid-derived suppressor cells (MDSCs) and thus is a negative regulator of antitumor immune responses (D’Amico et al.). DKK-1 from thrombocytes is an important regulator of leukocyte infiltration and induces Th2 cell polarization and potentiates Th2 cell cytokine expression (Chae et al.). DKK-1 has also been shown to drive cardiac and retinal differentiation from induced pluripotent stem (iPS) cells (Lian et al.). Protein contains a His-residue tag at the carboxyl end of the polypeptide chain.
(A) The biological activity of Human Recombinant DKK-1 was tested by its ability to inhibit Wnt3a induced alkaline phosphatase production by C3H10T1/2 cells. Alkaline phosphatase production was measured using a fluorometric assay method. The EC50 is defined as the effective concentration of the growth factor at which alkaline phosphatase production is at 50% of maximum. The EC50 in the above example is less than 4 μg/mL.
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