Human LRP-6 Biotinylated Antibody Summary
Ala20-Pro1368
Accession # O75581
Applications
Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website.
Reconstitution Calculator
Preparation and Storage
- 12 months from date of receipt, -20 to -70 °C as supplied.
- 1 month, 2 to 8 °C under sterile conditions after reconstitution.
- 6 months, -20 to -70 °C under sterile conditions after reconstitution.
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. Both LRP-5 and LRP-6 are type I transmembrane proteins that function as co-receptors with Frizzled (FZD) in the canonical Wnt signaling pathway (1, 2). LRP-6 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). LRP-6 has also been shown to interact with the Dickkopf proteins (DKKs), which are modulators of Wnt signaling (6-8). Binding of DKK-1 to LRP-6 dissociates LRP-6 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 LRP-6, 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 LRP-6-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).
- Howell, B.W. and J. Herz (2001) Curr. Op. Neurobiology 11:74.
- Pinson, K.I. et al. (2000) Nature 407:535.
- Brown, S.D. et al. (1998) Biochem. Biophys. Res. Commun. 248:879.
- Tamai, K. et al. (2000) Nature 407:530.
- Schweizer, L. and H. Varmus (2003) BMC Cell Biology 4:4.
- Mao, B. et al. (2001) Nature 411:321.
- Semenov, M.V. et al. (2001) Curr. Biol. 11:951.
- Bafico, A. et al. (2001) Nature Cell Biol. 3:683.
- Zorn, A.M. (2001) Curr. Biol. 11:R592.
- Mao, B. et al. (2002) Nature 417:664.
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