描述：
Dickkopf related protein 1 (Dkk-1) is the founding member of the Dickkopf family of proteins
that includes Dkk-1, -2, -3, -4, and a related protein, Soggy. Dkk proteins are secreted proteins
that contain two conserved cysteinerich domains separated by a linker region. Each domain
contains ten cysteine residues. Mature mouse Dkk-1 is a 40 kDa glycosylated protein that
shares 86%, 96%, 83% and 82% amino acid (aa) sequence identity with human, rat, rabbit and
bovine Dkk-1, respectively. It also shares 41% and 36% aa identity with human Dkk-2 and Dkk-4,
respectively. Dkk-1 and Dkk-4 are well documented antagonists of the canonical Wnt signaling
pathway. This pathway is activated by Wnt engagement of a receptor complex composed of the
Frizzled proteins and one of two low-density lipoprotein receptor-related proteins, LRP5 or
LRP6. Dkk-1 antagonizes Wnt by forming ternary complexes of LRP5/6 with Kremen1 or
Kremen2.Dkk-1/LRP6/Krm2 complex internalization has been shown to downregulate Wnt
signaling. Dkk-1 is expressed throughout development and antagonizes Wnt-7a during limb
development. Other sites of expression include developing neurons, hair follicles and the
retina of the eye. The balance between Wnt signaling and Dkk-1 inhibition is critical for bone
formation and homeostasis. Insufficient or excess Dkk-1 activity in bone results in increased
or decreased bone density, respectively. In adults, Dkk-1 is expressed in osteoblasts and
osteocytes, and neurons. Cerebral ischemia induces Dkk-1 expression, which contributes
to neuronal cell death.
原厂资料：
Dickkopf related protein 1 (Dkk-1) is the founding member of the Dickkopf family of proteins
that includes Dkk-1, -2, -3, -4, and a related protein, Soggy. Dkk proteins are secreted proteins
that contain two conserved cysteinerich domains separated by a linker region. Each domain
contains ten cysteine residues. Mature mouse Dkk-1 is a 40 kDa glycosylated protein that
shares 86%, 96%, 83% and 82% amino acid (aa) sequence identity with human, rat, rabbit and
bovine Dkk-1, respectively. It also shares 41% and 36% aa identity with human Dkk-2 and Dkk-4,
respectively. Dkk-1 and Dkk-4 are well documented antagonists of the canonical Wnt signaling
pathway. This pathway is activated by Wnt engagement of a receptor complex composed of the
Frizzled proteins and one of two low-density lipoprotein receptor-related proteins, LRP5 or
LRP6. Dkk-1 antagonizes Wnt by forming ternary complexes of LRP5/6 with Kremen1 or
Kremen2.Dkk-1/LRP6/Krm2 complex internalization has been shown to downregulate Wnt
signaling. Dkk-1 is expressed throughout development and antagonizes Wnt-7a during limb
development. Other sites of expression include developing neurons, hair follicles and the
retina of the eye. The balance between Wnt signaling and Dkk-1 inhibition is critical for bone
formation and homeostasis. Insufficient or excess Dkk-1 activity in bone results in increased
or decreased bone density, respectively. In adults, Dkk-1 is expressed in osteoblasts and
osteocytes, and neurons. Cerebral ischemia induces Dkk-1 expression, which contributes
to neuronal cell death.
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