Human Phospho-LRP-6 (S1490) Antibody

LRP6 (Low-density lipoprotein receptor-related protein 6) is a 200-210 kDa member of the LDLR family of proteins. It is widely expressed, and serves as a coreceptor for both Wnt and parathyroid hormone. In the Wnt system, LRP6 associates with select Fzd multipass receptors; in the PTH system, LRP6 complexes with PTHR1. Mature human LRP6 is a 1594 amino acid (aa) type I transmembrane glycoprotein. It contains a 1351 aa extracellular region (aa 20-1370) plus a 220 aa cytoplasmic domain (aa 1394-1613). The cytoplasmic domain contains two palmitoylation sites, one ubiquitination residue, and multiple phosphorylation motifs. Ser1490 is a key residue that impacts multiple activities. It undergoes both constitutive and receptor activation-induced phosphorylation. At least three enzymes likely act at this site, including PKA (associated with PTHR1), GSK-3 (associated with Fzd) and Cyclin Y/PFTK1 (associated with G2/M of the cell cycle). In general, Ser1490 phosphorylation results in beta-catenin stabilization, followed by either gene transcription or beta-catenin binding to centrosomes.