• Purity

  >90%, 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.  

• Activity

  Measured by its binding ability in a functional ELISA. rmLRP-6 binds rhDkk-1, biotin with an apparent K    _D <15 nM. Biotinylated rmWnt-3a immobilized on a streptavidin-coated plate at 1 µg/mL can bind rmLRP-6 with a linear range of 0.2-10 µg/mL.  

• Source

  Mouse myeloma cell line, NS0-derived Ala20-Pro1368, with a C-terminal 6-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Ala20

• Predicted Molecular Mass

  152.6 kDa

• SDS-PAGE

  170 kDa, reducing conditions

Background: LRP-6

The low-density lipoprotein (LDL) receptor-related protein 5 (LRP-5) and LRP-6 constitute a distinct subgroup of the LDL receptor family (1). Both LRP-5 and LRP-6 are type I transmembrane proteins that function as Wnt co-receptors with Frizzled proteins (FZD) (2, 3, 4). The mouse LRP-6 cDNA encodes a 1613 amino acid (aa) residue precursor including a 19 aa signal sequence, 1351 aa extracellular domain (ECD), a 23 aa transmembrane (TM) segment, and a 20 aa cytoplasmic domain (5). The ECD contains 20 YWTD motif-containing LDLR-B domains, fourEGF-like repeats, and three cysteine-rich LDLR-A repeats. The ECD of mouse LRP-6 shares 71% aa sequence identity with the ECD of mouse LRP-5 and 98% aa sequence identity with the ECD of human, rat, and canine LRP-6. The intracellular region of LRP-6 contains repeated PPPSP motifs. When the Ser/Thr in these motifs are phosphorylated, LRP-6 can interact with Axin and propagate canonical Wnt signal transduction (6, 7). LRP-6 forms inactive homodimers via its YWTD-EGF domains (8). Wnt binding to FZD and subsequent association with LRP-6 lead to activating conformational changes in LRP-6 cytoplasmic domains (8). LRP-6 can also interact directly with the Dickkopf (Dkk), sclerostin, and Wise proteins which are modulators of Wnt signaling (9 - 14). Formation of a ternary complex of LRP-6, Dkk-1, and Kremen triggers the internalization of the complex and removal LRP-6 from the cell surface. LRP-5 and LRP-6 share overlapping functions in diverse embryonic developmental processes (15).

• References:

1. Schneider, W.J. and J. Nimpf (2003) Cell Mol Life Sci. 60:892.

2. He, X. et al. (2004) Development 131:1663.

3. Seto, E.S. and H.J. Bellen (2004) Trends Cell Biol. 14:45. 

4. Pinson, K.I. et al. (2000) Nature 407:535. 

5. Brown, S.D. et al. (1998) Biochem. Biophys. Res. Commun. 248:879.

6. Tamai, K. et al. (2000) Nature 407:530. 

7. Tamai, K. et al. (2004) Mol. Cell 13:149. 

8. Liu, G. et al. (2003) Mol. Cell. Biol. 23:5825.

9. Mao, B. et al. (2001) Nature 411:321.

10. Semenov, M.V. et al. (2001) Curr. Biol. 11:951.

11. Bafico, A. et al. (2001) Nat. Cell Biol. 3:683.

12. Li, X. et al. (2005) J. Biol. Chem. 280:19883.

13. Semenov, M. et al. (2005) J. Biol. Chem. 280:26770.

14. Itasaki, N. et al. (2003) Development 130:4295.

15. Kelly, O. et al. (2004) Development 131:2803.

• Long Name:

  LDL Receptor-related Protein 6

• Entrez Gene IDs:

  4040 (Human); 16974 (Mouse)

• Alternate Names:

  ADCAD2; FLJ90062; FLJ90421; low density lipoprotein receptor-related protein 6; low-density lipoprotein receptor-related protein 6; LRP6; LRP-6