DKK1 (human, recombinant)

Dickkopf-related Protein 1

Dickkopf-related protein 1 (DKK1) is a glycoprotein and a member of the DKK family of proteins.{56080} DKK1 contains a signal sequence and N- and C-terminal conserved cysteine-rich domains connected by a non-conserved linker region. The C-terminal domain contains a colipase fold domain that is sufficient for its biological activity. DKK1 is a secretory protein that is expressed in osteoblasts, osteocytes, skin, placenta, prostate, and platelets.{56081} It binds to lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent it from forming a β-catenin-stabilizing complex with Wnt and Frizzled, thus inactivating Wnt-β-catenin signaling. In the presence of the DKK1 co-receptor Kremen, LRP6 is endocytosed to prevent its interaction with Wnt and Frizzled. DKK1 is also a target of the β-catenin-TCF transcription factor complex forming a negative feedback loop for Wnt signaling.{56082} Dkk1 knockout in mice is embryonic lethal with embryos lacking anterior head structures, as well as having ectopic and fused digits and fused vertebrae.{56083} Mice heterozygous for Dkk1 have increased bone density, and overexpression of Dkk1 in mice leads to osteopenia.{56080} DKK1 expression is increased in a variety of cancers and plasma levels are correlated with the development of osteolytic lesion formation in patients with multiple myeloma.{56080,56084} Activation of DKK1 in cancer cells in vitro and in vivo can inhibit growth, however, DKK1 inhibition can reduce tumor growth in certain mouse xenograft models, suggesting a cell- or tissue-specific effect.{56084,56085} DKK1 expression is increased in the brain of Alzheimer’s disease mouse models, cerebrospinal fluid and plasma of patients with Alzheimer’s disease, and in postmortem brain derived from Alzheimer’s disease patients.{56086} Cayman’s DKK1 (human, recombinant) protein can be used for cell-based assay applications. This protein consists of 235 amino acids, has a calculated molecular weight of 25.8 kDa, and a predicted N-terminus of Thr32 or Ser35 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is approximately 45 kDa due to glycosylation.

-80

-80

Lyophilized from sterile PBS, pH 7.4, with 5% Trehalose, 5% Mannitol, and 0.01% Tween-80

365

≥90% estimated by SDS-PAGE