Cell Signaling Technology

Product Pathways - Wnt / Hedgehog / Notch

Phospho-LRP6 (Ser1490) Antibody #2568

Applications Reactivity Sensitivity MW (kDa) Source
W IP H (M) Endogenous 180, 210 Rabbit

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human  M=Mouse
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

Phospho-LRP6 (Ser1490) Antibody detects endogenous levels of LRP6 protein when phosphorylated at serine 1490. It is expected, although not yet confirmed, to also detect endogenous levels of LRP5 protein when phosphorylated at serine 1493 (corresponding to serine 1490 in LRP6).

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser1490 of human LRP6. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of total cell lysates from HeLa cells untreated, treated 5 hours with conditioned medium (CM) from L cells, or treated 5 hours with conditioned medium from L cells overexpressing Wnt3a, using Phospho-LRP6 (Ser1490) Antibody #2568.

Background

LRP5 and LRP6 are single-pass transmembrane proteins belonging to the low-density lipoprotein receptor (LDLR)-related protein family. Unlike other members of the LDLR family, LRP5 and LRP6 have four EGF and three LDLR repeats in the extracellular domain, and proline-rich motifs in the cytoplasmic domain (1). They function as co-receptors for Wnt and are required for the canonical Wnt/β-catenin signaling pathway (2,3). LRP5 and LRP6 are highly homologous and have redundant roles during development (4,5). The activity of LRP5 and LRP6 can be inhibited by the binding of some members of the Dickkopf (DKK) family of proteins (6,7). Upon stimulation with Wnt, LRP6 is phosphorylated at multiple sites including Thr1479, Ser1490, and Thr1493 by kinases such as GSK-3 and CK1 (8-10). Phosphorylated LRP6 recruits axin to the membrane and presumably activates β-catenin signaling (8-10).

  1. Brown, S.D. et al. (1998) Biochem. Biophys. Res. Commun. 248, 879-888.
  2. Pinson, K.I. et al. (2000) Nature 407, 535-538.
  3. Tamai, K. et al. (2000) Nature 407, 530-535.
  4. Kelly, O.G. et al. (2004) Development 131, 2803-2815.
  5. He, X. et al. (2004) Development 131, 1663-1677.
  6. Semënov, M.V. et al. (2001) Curr Biol 11, 951-61.
  7. Bafico, A. et al. (2001) Nat. Cell Biol. 3, 683-668.
  8. Tamai, K. et al. (2004) Mol. Cell 13, 149-156.
  9. Zeng, X. et al. (2005) Nature 438, 873-877.
  10. Davidson, G. et al. (2005) Nature 438, 867-872.

Application References

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This product is intended for research purposes only. The product is not intended to be used for therapeutic or diagnostic purposes in humans or animals.

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