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Beschreibung

Dickkopf-related protein 2 (UniProt: Q9UBU2, also known as Dickkopf-2, DKK2, Dkk-2, hDkk-2) is encoded by the DKK2 (also known as UNQ682/PRO1316) gene (Gene ID: 27123) in human. DKK2 is a member of the Dickkopf family that is expressed in heart, brain, skeletal muscle, and lung. It is synthesized with a signal peptide (aa 1-33) that is subsequently cleaved off in the mature form. DKK2 is reported to antagonize canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. Its C-terminal cysteine-rich domain mediates its interaction with LRP5 and LRP6. It plays play an important role in vertebrate development, where it locally inhibits Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. DKK2 secreted by tumor cells is shown to act on cytotoxic lymphocytes and inhibit STAT5 signaling by blocking STAT5 nuclear localization via LRP5, independent of LRP6. Loss of DKK2 is reported to activate natural killer (NK) cells and CD8+ T cells in tumors that can delay tumor progression and enhance the effects of PD-1 blockade. (Ref.: Xiao, Q., et al. (2018). Nat. Med. 24(3): 262-270).