Dickkopf WNT Signaling Pathway Inhibitor 1 (DKK1)

DKK-1 is a secreted glycoprotein that plays a significant role in embryonic development and various disease processes. It is a glycoprotein consisting of 255-350 amino acids with a molecular weight of 24-29 kDa, containing two cysteine-rich domains that mediate protein-protein interactions. The name "Dickkopf" comes from German, meaning "stubborn person" or literally "thick head," coined in a 1998 Nature paper by Glinka et al. in reference to DKK1's role in inducing head formation during embryogenesis.

Other names

Dickkopf-related protein 1Dickkopf-1Dkk-1

DKK1 primarily functions as an antagonist of the canonical Wnt signaling pathway by binding to the LRP6 co-receptor, preventing its interaction with Wnt proteins, and forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. This inhibition plays a key role in heart, head, and forelimb development during anterior morphogenesis of the embryo. DKK1 can also function through a non-canonical pathway by binding to cytoskeleton-associated protein 4 (CKAP4), which can promote cancer cell proliferation. Therapeutic strategies targeting DKK1 aim to inhibit its activity, for example, anti-DKK1 antibodies have shown inhibition of multiple myeloma cell proliferation.