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Recombinant Human LRP-6 Fc Chimera Protein, CF

Catalog # 1505-LR | R&D Systems, Inc. a Bio-Techne Brand
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1505-LR-025

Key Product Details

Source

NS0

Accession #

Structure / Form

Disulfide-linked homodimer

Conjugate

Unconjugated

Applications

Binding Activity

Product Specifications

Source

Mouse myeloma cell line, NS0-derived human LRP-6 protein
Human LRP-6
(Ala20 - Pro1368)
Accession # O75581
IEGRMD Human IgG1
(Pro100 - Lys330)
N-terminus C-terminus

Purity

>80%, by SDS-PAGE under reducing conditions and visualized by silver stain.

Endotoxin Level

<0.1 EU per 1 μg of the protein by the LAL method.

N-terminal Sequence Analysis

Ala20

Predicted Molecular Mass

180 kDa (monomer)

SDS-PAGE

200 kDa, reducing conditions

Activity

Measured by its binding ability in a functional ELISA.
rhLRP-6/Fc Chimera binds rhDkk-1, biotin with an apparent KD <25 nM.

Biotinylated rmWnt-3a immobilized on a streptavidin-coated plate at 1 µg/mL can bind rhLRP-6/Fc Chimera with a linear range of 0.2-10 µg/mL.
Optimal concentrations should be determined by each laboratory for each application.

Formulation, Preparation and Storage

1505-LR
Formulation Lyophilized from a 0.2 μm filtered solution in PBS.
Reconstitution
Reconstitute at 200 μg/mL in sterile PBS.

Reconstitution Buffer Available:
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Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below.
Stability & Storage Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -20 to -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, -20 to -70 °C under sterile conditions after reconstitution.

Background: LRP-6

The low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and LRP6 constitute a distinct subgroup of the LDL receptor family. Both LRP5 and LRP6 are type I transmembrane proteins that function as co-receptors with Frizzled (FZD) in the canonical Wnt signaling pathway (1, 2). LRP6 cDNA encodes a 1613 amino acid residue (aa) precursor with a 19 aa signal sequence, a 1353 aa extracellular region, a 23 aa transmembrane (TM) segment and a 218 aa cytoplasmic domain (3). The extracellular region contains four N-terminal cysteine-rich EGF-like repeats, followed by three cysteine-rich LDLR repeats. This pattern of the EGF and LDLR repeat arrangement is different than that typically found in other LDL receptor family proteins. The intracellular region of LRP6 contains protein-protein interaction motifs and is required for canonical Wnt signal transduction (4). Human LRP-6 shares 98% and 74% aa sequence identity with mouse LRP-6 and human LRP-5, respectively. Based on the current model, canonical Wnt signaling requires the interaction of Wnt with FZD and LRP to form a trimeric complex which signals downstream to stabilize cytoplasmic  beta-catenin. The stabilized beta-catenin is then translocated to the nucleus where it complexes with the transcription factor LEF/TCF to regulate the transcription of target genes (5). LRP6 has also been shown to interact with the Dickkopf proteins (DKKs), which are modulators of Wnt signaling (6 - 8). Binding of DKK-1 to LRP6 dissociates LRP6 from FZD, and antagonizes the formation of the functional receptor complex. On cells where the transmembrane proteins Kremens are also present, a ternary complex of LRP6, DKK-1 and Kremen is formed to trigger the internalization of the complex and removal LRP6 from the cell surface. Thus, DKK-1 and Kremen function synergistically to antagonize LRP6-mediated Wnt activity. Although DKK-2 also functions as a Wnt antagonist on cells that express Kremen, DKK-2 binding to LRP-6 in the absence of Kremen activates rather than inhibits LRP mediated beta-catenin signaling (9, 10).

References

  1. Howell, B.W. and J. Herz (2001) Curr. Op. Neurobiology 11:74.
  2. Pinson, K.I. et al. (2000) Nature 407:535.
  3. Brown, S.D. et al. (1998) Biochem. Biophys. Res. Commun. 248:879.
  4. Tamai, K. et al. (2000) Nature 407:530.
  5. Schweizer, L. and H. Varmus (2003) BMC Cell Biology 4:4.
  6. Mao, B. et al. (2001) Nature 411:321.
  7. Semenov, M.V. et al. (2001) Curr. Biol. 11:951.
  8. Bafico, A. et al. (2001) Nature Cell Biol. 3:683.
  9. Zorn, A.M. (2001) Curr. Biol. 11:R592.
  10. Mao, B. et al. (2002) Nature 417:664.

Long Name

LDL Receptor-related Protein 6

Alternate Names

ADCAD2, FLJ90062, FLJ90421, LRP6

Entrez Gene IDs

4040 (Human); 16974 (Mouse)

Gene Symbol

LRP6

UniProt

Additional LRP-6 Products

Product Documents for Recombinant Human LRP-6 Fc Chimera Protein, CF

Certificate of Analysis

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Note: Certificate of Analysis not available for kit components.

Product Specific Notices for Recombinant Human LRP-6 Fc Chimera Protein, CF

For research use only

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