描述：
Dickkopf related protein 2 (Dkk-2) is a member of the Dickkopf family of secreted Wnt
modulators. Dkk proteins contain a signal peptide and two conserved cysteine-rich domains
that are separated by a linker region. The second cysteinerich domain mediates Dkk-2 binding
activities, and its interaction with LRP beta propellers has been mapped. The 226 aa, 35 kDa
mature mouse Dkk-2 shares 99%, 96%, 96%, 96% and 94% aa identity with rat, human, dog,
horse and cow Dkk-2, respectively, and can activate the canonical Wnt signaling pathway in
Xenopus embryos. Dkk proteins modify Wnt engagement of a receptor complex composed
of a Frizzled protein and a lowdensity lipoprotein receptorrelated protein, either LRP5 or
LRP6. When LRP6 is overexpressed, direct high-affinity binding of Dkk-2 to LRP can enhance
canonical Wnt signaling. However, when Dkk-2 and LRP6 form a ternary complex with
Kremen2, Wnt signaling is inhibited due to internalization of Dkk-2/LRP6/Krm2 complexes.
Thus, depending on the cellular context, Dkk-2 can either activate or inhibit canonical Wnt
signaling. In contrast, binding of Dkk-1 or Dkk4 to LRP is consistently antagonistic. Dkk proteins
are expressed in mesenchymal tissues and control epithelial transformations. Dkk-2 expression
has been studied most in bone and eye, although it is expressed as early as periimplantation in
mice. Mouse Dkk-1 or Dkk-2 deficiencies have opposite effects on bone homeostasis, despite
downregulating Wnt antagonism in both cases. Dkk-2 expression is induced by Wnts in bone,
and is thought to enhance bone density by promoting terminal differentiation of osteoblasts
and mineral deposition. In contrast, Dkk-1 negatively regulates late osteoblast proliferation,
which limits bone density. Dkk-2deficient mice are blind, exhibiting faulty differentiation of
corneal epithelium and ectopic blood vessels in the periocular mesenchyme.
原厂资料：
Dickkopf related protein 2 (Dkk-2) is a member of the Dickkopf family of secreted Wnt
modulators. Dkk proteins contain a signal peptide and two conserved cysteine-rich domains
that are separated by a linker region. The second cysteinerich domain mediates Dkk-2 binding
activities, and its interaction with LRP beta propellers has been mapped. The 226 aa, 35 kDa
mature mouse Dkk-2 shares 99%, 96%, 96%, 96% and 94% aa identity with rat, human, dog,
horse and cow Dkk-2, respectively, and can activate the canonical Wnt signaling pathway in
Xenopus embryos. Dkk proteins modify Wnt engagement of a receptor complex composed
of a Frizzled protein and a lowdensity lipoprotein receptorrelated protein, either LRP5 or
LRP6. When LRP6 is overexpressed, direct high-affinity binding of Dkk-2 to LRP can enhance
canonical Wnt signaling. However, when Dkk-2 and LRP6 form a ternary complex with
Kremen2, Wnt signaling is inhibited due to internalization of Dkk-2/LRP6/Krm2 complexes.
Thus, depending on the cellular context, Dkk-2 can either activate or inhibit canonical Wnt
signaling. In contrast, binding of Dkk-1 or Dkk4 to LRP is consistently antagonistic. Dkk proteins
are expressed in mesenchymal tissues and control epithelial transformations. Dkk-2 expression
has been studied most in bone and eye, although it is expressed as early as periimplantation in
mice. Mouse Dkk-1 or Dkk-2 deficiencies have opposite effects on bone homeostasis, despite
downregulating Wnt antagonism in both cases. Dkk-2 expression is induced by Wnts in bone,
and is thought to enhance bone density by promoting terminal differentiation of osteoblasts
and mineral deposition. In contrast, Dkk-1 negatively regulates late osteoblast proliferation,
which limits bone density. Dkk-2deficient mice are blind, exhibiting faulty differentiation of
corneal epithelium and ectopic blood vessels in the periocular mesenchyme.
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