Y00701 Recombinant Human DKK1

产品信息(Information)：

背景介绍(Background)：

This protein is a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This protein plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this protein has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]

Dickkopf-1 (DKK1) is a secretory glycoprotein with two conserved domains rich in cysteine and a connecting region of 50–55 amino acids. The full length of human DKK1 gene is 1815kb, which is located on chromosome 10q11.2.26. DKK1 plays a role in promoting angiogenesis during tumorigenesis and inflammation. DKK1 was initially studied for its role in Xenopus head development, and the authors discovered DKK1 was secreted by the Spemann’s organizer, to inhibit the Wnt signaling pathway in Xenopus embryos. The Spemann’s organizer is initially activated by the Wnt signaling pathway during early embryogenesis, and during late embryogenesis it is deactivated by Wnt inhibitors such as DKK1. DKK1 participates in the canonical Wnt (β-catenin dependent) pathway by acting as a competitive inhibitor of Wnt. DKK1 binds to, stabilizes and accumulates LRP6 on cell surfaces. The C-terminal of DKK1 contains a colipase fold and is essential for the interaction between DKK1 and LRP6, Kremen1 and Kremen2 co-receptors. Kremen2 binding initiates formation of a ternary complex with DKK1 and LRP6 that induces endocytosis or clearance of LRP6 from the cell membrane, preventing further Wnt-LRP5/6 interaction. This facilitates ubiquitin binding to β-catenin by Skp and β-TrCP and, therefore, subsequent degradation of β-catenin by a proteasome. This pathway is significant to cancer development because in the absence of DKK1, the canonical Wnt pathway is unregulated and leads to excessive cell proliferation through the upregulation of β-catenin.

图 DKK1结合LRP5/6以拮抗Wnt信号通路

制剂(Formulation)：

Lyophilized from 0.22 μm filtered solution in PBS，5%mannital，0.01% Tween80 pH7.4. 

质量控制(Quality Control)：

Purity: ≥ 95% as determined by reducing SDS-PAGE.    

Endotoxin: ≤10 EU/mg  as determined by LAL test.

保存(Storage)：

Use a manual defrost freezer and avoid repeated freeze - thaw cycles.
12 months from date of receipt, -20 to -70℃ as supplied.
1 month, 2 to 8℃ under sterile conditions after reconstitution.
6 months, -20 to -70℃ under sterile conditions after reconstitution.

FOR RESEARCH USE ONLY

参考文献：

[1] Zhu G, et al. 2021. Cancer Manag Res. 13:659-675.

[2] Igbinigie E, et al. 2019. Clin Chim Acta. 488:226-234.