DKK-1 is a member of the DKK protein family which also includes DKK-2, DKK-3 and DKK-4. DKK-1 was originally identified as a Xenopus head forming molecule that behaves as an antagonist for Wnt signaling. Subsequent studies have shown that DKK-1 and DKK-4 play an important regulatory role in the Wnt /β-catenin signaling pathway by forming inhibitory complexes with LDL receptor-related proteins 5 and 6 (LRP5 and LRP6), which are essential components of the Wnt/β catenin signaling system. LPR5 and LPR6 are single-pass transmembrane proteins that appear to act as co-receptors for Wnt ligands involved in the Wnt/β catenin signaling cascade. It has been suggested that by inhibiting Wnt/β catenin signaling, which is essential for posterior patterning in vertebrates, DKK-1 permits anterior development. This notion is supported by the finding that mice deficient of DKK-1 expression lack head formation and die during embryogenesis. Recombinant human DKK-1 expressed in human 293 cells is a 35-40 kDa glycoprotein containing 235 amino-acid residues.
DKK1 (dickkopf WNT signaling pathway inhibitor 1) is one of the four members of the evolutionary conserved small gene family called DKK. DKKs are secreted glycoprotein composed of 255–350 amino acids (aa) and a molecular weight between 24 and 29kDa for DKK1. All DKKs are composed of two conserved cysteine-rich domains and a leader peptide. They also contain an N-terminal cysteine-rich domain, DKK_N, and a colipase fold domain, which are connected by a non-conserved linker region of around 50-55 amino acids in DKK1. DKK1 is the founding member of DKK family, and was first identified in Xenopus as an embryonic head inducer and Wnt antagonist.
DKK1 (dickkopf WNT signaling pathway inhibitor 1) functions as a pure inhibitor of Wnt signaling, and was identified as an essential factor for head induction during early Xenopus embryogenesis by suppressing Wnt signaling. In skin, this protein plays a role in determining the pigmentation pattern of the human hand. In colon cancer cells, this protein is inactivated by CpG island promoter hypermethylation. Mesenchymal stem cells (MSCs) have an anti-proliferative effect on cancer cells, as they secrete DKK1 which blocks Wnt signaling.
Sterile filtered through a 0.2 micron filter. Lyophilized from 1X PBS, pH 7.5.
Centrifuge the vial prior to opening. Reconstitute in water to a concentration of 0.1-1.0 mg/mL. Do not vortex. This solution can be stored at 2-8°C for up to 1 week. For extended storage, it is recommended to further dilute in a buffer containing a carrier protein (example 0.1% BSA) and store in working aliquots at -20°C to -80°C.