Search results for LRP6

Showing 22 results out of 40

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Protein (6 results from a total of 8)

Identifier: R-HSA-206252
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: LRP6: O75581
Identifier: R-HSA-5368481
Species: Homo sapiens
Compartment: early endosome membrane
Primary external reference: UniProt: O75581
Identifier: R-HSA-206156
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: LRP6: O75581
Identifier: R-HSA-5368496
Species: Homo sapiens
Compartment: early endosome membrane
Primary external reference: UniProt: O75581
Identifier: R-HSA-1458894
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: O75581
Identifier: R-HSA-205884
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: O75581

Reaction (6 results from a total of 22)

Identifier: R-HSA-5368586
Species: Homo sapiens
Compartment: plasma membrane, early endosome membrane
Binding of DKK1 to LRP6 induces the clathrin-mediated endocytosis of LRP6, preventing the WNT3-dependent phosphorylation of LRP and thereby attenuating WNT signaling (Sakane et al, 2010; Yamamoto et al, 2008). The DKK:LRP:KRM complex traffics to the early endosome in a RAB5-dependent manner. The LRP receptor can subsequently recycle back to the plasma membrane in a RAB11-dependent manner, while DKK may be degraded in the lysosome (Sakane et al, 2010)
Identifier: R-NUL-209104
Species: Homo sapiens, Xenopus tropicalis
Compartment: cytosol, plasma membrane
Frog CKIgamma further phosphorylates Human LRP6 in the receptor complex
Identifier: R-HSA-5368596
Species: Homo sapiens
Compartment: plasma membrane, early endosome membrane
After stimulation by WNT3A, FZD5 and phosphorylated LRP6 are internalized from lipid rafts in a caveolin- and RAB5-dependent manner (Yamamoto et al, 2006; Yamamoto et al, 2008). Recruitment of CAV1 to the activated receptor complex inhibits the binding of beta-catenin to AXIN in the destruction complex, resulting in the accumulation of cytosolic beta-catenin and the induction of WNT-dependent signaling (Yamamoto et al, 2006; Yamamoto et al, 2008).
Identifier: R-NUL-1458871
Species: Homo sapiens, Mus musculus
Compartment: extracellular region
HEK293 cells were transiently transfected with constructs encoding the extracellular regions of mouse Frizzled8 and human LRP6, and co-immunoprecipitations were performed from conditioned medium. The association between mFzd8CRD and LRP6N was dependent on mWnt1.
Identifier: R-HSA-3772436
Species: Homo sapiens
Compartment: cytosol, plasma membrane
Stimulation of the WNT pathway controls the activity of PIP5KB in a FZD- and DVL-dependent manner (Pan et al, 2008; Bilic et al, 2007; Cong et al, 2004; Qin et al, 2009). Activation of PIP5KB results in the formation of PI(4,5)P2 at the plasma membrane, which is required through an unclear mechanism for the phosphorylation of LRP6 at serine 1490, LRP6 aggregation into 'signalosomes' and LRP6 phosphorylation at threonine 1479. These events are required for the recruitment of AXIN to the plasma membrane (Pan et al, 2008; Qin et al, 2009).
Identifier: R-HSA-3772434
Species: Homo sapiens
Compartment: cytosol
DVL1 and 3 have been shown to co-immunoprecipitate with PIP5KB in HEK293 cells. This interaction is mediated by the N-terminal half of the kinase and the PDZ and DIX domain of DVL and recruits PIPK5B to the receptor complex. The interaction of DVL and PIP5KB is required for the WNT3A-dependent phosphorylation of LRP6 at serine 1490 and threonine 1479, as well as and the subsequent formation of the signalosome and recruitment of AXIN (Pan et al, 2008).

Complex (4 results from a total of 4)

Identifier: R-HSA-5368521
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5368519
Species: Homo sapiens
Compartment: early endosome membrane
Identifier: R-NUL-9608501
Species: Homo sapiens, Xenopus tropicalis
Compartment: plasma membrane
Identifier: R-NUL-206831
Species: Homo sapiens, Xenopus tropicalis
Compartment: plasma membrane

Pathway (4 results from a total of 4)

Identifier: R-HSA-3772470
Species: Homo sapiens
Compartment: extracellular region
Several unrelated families of secreted proteins antagonize WNT signaling. Secreted frizzled-related proteins (sFRPs) have a cysteine rich domain (CRD) that is also found in FZD and ROR receptors, while WNT inhibitory factor (WIF) proteins contain a WIF domain also present in the WNT-receptor RYK. Both these classes of secreted WNT antagonists inhibit signaling by binding to WNTs and preventing their interaction with the FZD receptors. sFRPs may also able to bind the receptors, blocking ligand binding (Bafico et al, 1999; reviewed in Kawano and Kypta, 2003). The interaction of WIF and sFRPs with WNT ligand may also play a role in regulating WNT diffusion and gradient formation (reviewed in Boloventa et al, 2008).

Dickkopf (DKK) and Sclerostin (SOST) family members, in contrast, antagonize WNT signaling by binding to LRP5/6. There are four DKK family members in vertebrates; the closely related DKK1, 2 and 4 proteins have been shown to have roles in WNT signaling, while the more divergent DKK3 appears not to (Glinka et al, 1998; Fedi et al, 1999; Mao et al, 2001; Semenov et al, 2001; reviewed in Niehrs, 2006). Secreted DKK proteins bind to LRP6 in conjunction with the single-pass transmembrane proteins Kremen 1 and 2, and this interaction is thought to disrupt the WNT-induced FZD-LRP5/6 complex. In some cases, DKK2 has also been shown to function as a WNT agonist (reviewed in N (reviewed in Niehrs, 2006).
Like DKK proteins, SOST binds LRP5/6 and disrupts WNT-dependent receptor activation (Semenov et al, 2005).
Identifier: R-HSA-4411364
Species: Homo sapiens
Compartment: nucleoplasm
The genes regulated by beta-catenin and TCF/LEF are involved in a diverse range of functions in cellular proliferation, differentiation, embryogenesis and tissue homeostasis, and include transcription factors, cell cycle regulators, growth factors, proteinases and inflammatory cytokines, among others (reviewed in Vlad et al, 2008). A number of WNT signaling components are themselves positively or negatively regulated targets of TCF/LEF-dependent transcription, establishing feedback loops to enhance or restrict signaling (see for instance, Khan et al 2007; Chamorro et al, 2005; Roose et al, 1999; Lustig et al, 2002). Other than a few of these general feedback targets (e.g. Axin2), most target genes are cell- and/or tissue-specific. A list of WNT/beta-catenin-dependent target genes is maintained at http://www.standford.edu/group/nusselab/cgi-bin/wnt/target_genes.
Identifier: R-HSA-4641262
Species: Homo sapiens
Upon stimulation with WNT ligand, AXIN and GSK3beta are recruited to the plasma membrane through interaction with DVL (Tamai et al, 2004; Mao et al, 2001; reviewed in He et al, 2004). Polymerization of membrane-associated DVL and GSK3beta- and CSNK1-mediated phosphorylation of LRP5/6 establish a feed-forward mechanism for enhanced membrane recruitment of AXIN upon WNT signaling (Tamai et al, 2004; Cong et al, 2004; Zeng et al, 2005; Bilic et al, 2007). In Xenopus oocytes, but not necessarily all sytems, AXIN is present in limiting concentrations and is considered rate limiting for the assembly of the destruction complex (Lee et al, 2003; Benchabane et al, 2008; Tan et al, 2012; reviewed in MacDonald et al, 2009). The recruitment of AXIN away from the destruction complex upon WNT stimulation effectively destabilizes the destruction complex and contributes to the accumulation of free beta-catenin (Kikuchi, 1999; Lee et al, 2003). AXIN association with the destruction complex is also regulated by phosphorylation. In the active destruction complex, AXIN is phosphorylated by GSK3beta; dephosphorylation by protein phosphatase 1 (PP1) or protein phosphatase 2A (PP2A) destabilizes the interaction of AXIN with the other components of the destruction complex and promotes its disassembly (Luo et al, 2007; Willert et al, 1999; Jho et al, 1999). Free AXIN is also subject to degradation by the 26S proteasome in a manner that depends on the poly-ADP-ribosylating enzymes tankyrase 1 and 2 (Huang et al, 2009).
Identifier: R-HSA-201688
Species: Homo sapiens
The three human Dishevelled (DVL) proteins play a central and overlapping role in the transduction of the WNT signaling cascade (Lee et al, 2008; reviewed in Gao and Chen 2010). DVL activity is regulated by phosphorylation, although the details are not completely worked out. DVL likely exists as a phosphoprotein even in the absence of WNT stimulation, and is further phosphorylated upon ligand binding. Casein kinase 1epsilon (CSNK1E), casein kinase 2 (CSNK2) and PAR1 have all been reported to phosphorylate DVL (Willert et al, 1997; Sun et al, 2001; Cong et al, 2004; Ossipova et al, 2005). Upon pathway activation, phosphorylated DVL translocates to the plasma membrane through an interaction between the DVL PDZ domain and the FZD KTxxxW motif (Wong et al, 2003; Umbhauer et al, 2000; Kikuchi et al, 2011). At the plasma membrane, DVL is believed to oligomerize through its DIX domain, providing a platform for AXIN recruitment; recruitment of AXIN is also facilitated by interaction with LRP (Schwarz-Romond et al, 2007; Mao et al, 2001). DVL interacts with phosphatidylinositol-4-kinase type II (PI4KII) and phophatidylinositol-4-phosphate 5-kinase type I (PIP5KI) to promote formation of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the membrane, which is required for the clustering and phosphorylation of LRP6 and the recruitment of AXIN (Pan et al, 2008; Qin et al, 2009).

Icon (2 results from a total of 2)

Species: Homo sapiens
Curator: Nicholas Norwitz
Designer: Sam Norwitz
LRP6 icon
Low-density lipoprotein receptor-related protein 6
Species: Homo sapiens
Curator: Nicholas Norwitz
Designer: Sam Norwitz
LRP6/FZD 02 icon
Representation of LRP6 and an alternative version of FZD
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