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LRP6 Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor- ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3- mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation. Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling. Forms a WNT-signaling complex formed of a WNT protein, a FZD protein and LRP5 or LRP6. Interacts (via the extracellular domain) with WNT1; the interaction is enhanced by prior formation of the Wnt/Fzd complex. Interacts (via the beta-propeller regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions 1 and 2) with WNT9B. Interacts with FZD5; the interaction forms a coreceptor complex for Wnt signaling and is inhibited by DKK1 and C1orf187. Interacts (via beta propeller region) with DKK1; the interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2. Interacts with C1orf187/DRAXIN; the interaction inhibits Wnt signaling. Interacts (via the phosphorylated PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell surface LRP6 signalsomes. Interacts with GRB10; the interaction prevents AXIN1 binding, thus negatively regulating the Wnt signaling pathway. Interacts (via the extracellular domain) with RSPO1; the interaction activates Wnt/beta-catenin signaling. Interacts (via the extracellular domain) with RSPO3 (via the cysteine rich domain); the interaction activates Wnt/beta-catenin signaling. Interacts (via the beta- propeller regions 1 and 2) with SOST; the interaction competes with DKK1 for binding for inhibiting beta-catenin signaling. Interacts with MESD; the interaction prevents the formation of LRP6 aggregates and targets LRP6 to the plasma membrane. Interacts (via the cytoplasmic domain) with CSNKIE; the interaction phosphorylates LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of beta-catenin. Interacts with MACF1. Decreased levels on WNT3A stimulation. Widely co-expressed with LRP5 during embryogenesis and in adult tissues. Belongs to the LDLR family. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral; Receptor, misc.
Chromosomal Location of Human Ortholog: 6 G1|6 65.37 cM
Cellular Component: caveola; cell soma; cell surface; cytoplasmic vesicle; early endosome; Golgi apparatus; membrane; plasma membrane; receptor complex; synapse
Molecular Function: apolipoprotein binding; frizzled binding; identical protein binding; kinase inhibitor activity; low-density lipoprotein receptor activity; protein binding; protein homodimerization activity; receptor binding; toxin transporter activity; Wnt receptor activity; Wnt-protein binding
Biological Process: anterior/posterior pattern formation; bone remodeling; cell migration involved in gastrulation; cell-cell adhesion; cerebellum morphogenesis; cerebral cortex cell migration; cerebral cortex development; convergent extension; dorsal/ventral axis specification; elevation of cytosolic calcium ion concentration; embryonic camera-type eye morphogenesis; embryonic digit morphogenesis; embryonic forelimb morphogenesis; embryonic hindlimb morphogenesis; embryonic limb morphogenesis; embryonic pattern specification; embryonic retina morphogenesis in camera-type eye; external genitalia morphogenesis; forebrain development; formation of radial glial scaffolds; gastrulation with mouth forming second; generation of neurons; generation of neurons in the forebrain; heart looping; limb morphogenesis; midbrain development; midbrain-hindbrain boundary development; morphogenesis of an epithelium; negative regulation of epithelial cell proliferation; negative regulation of fat cell differentiation; negative regulation of protein amino acid phosphorylation; negative regulation of protein kinase activity; negative regulation of Wnt receptor signaling pathway; neural crest cell differentiation; neural crest formation; neural tube closure; neural tube development; odontogenesis of dentine-containing teeth; palate development; positive regulation of apoptosis; positive regulation of bone resorption; positive regulation of cell cycle; positive regulation of mesenchymal cell proliferation; positive regulation of ossification; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; radial glial cell differentiation in the forebrain; regulation of cell proliferation; regulation of transcription, DNA-dependent; response to folic acid; retina morphogenesis in camera-type eye; skeletal morphogenesis; somitogenesis; synaptic transmission; thalamus development; Wnt receptor signaling pathway; Wnt receptor signaling pathway in forebrain neuroblast division; Wnt receptor signaling pathway through beta-catenin
Reference #:  O88572 (UniProtKB)
Alt. Names/Synonyms: C030016K15Rik; Cd; crooked; low density lipoprotein receptor-related protein 6; low density lipoprotein-related protein 6; Low-density lipoprotein receptor-related protein 6; LRP-6; Lrp6; OTTMUSP00000023469
Gene Symbols: Lrp6
Molecular weight: 180,255 Da
Basal Isoelectric point: 5.13  Predict pI for various phosphorylation states
CST Pathways:  ESC Pluripotency and Differentiation  |  Microtubule Dynamics  |  mTOR Signaling  |  Translation: eIF4E and p70S6K  |  Wnt/ß-Catenin Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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