Search results for LRP6

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Reaction (6 results from a total of 22)

Identifier: R-HSA-5210921
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Extracellular pagA (also known as PA83 - full length Protective Antigen - Petosa et al. 1997) produced by Bacillus anthracis binds to either of two isoforms of ANTXR1 (Anthrax Toxin Receptor 1, also known as TEM8 - Bradley et al. 2001; Liu and Leppla 2003) in the plasma membrane of a target human cell. The physiological ligand for ANTXR1 is not known nor are the physiological roles of the two ANTRX1 isoforms. Although ANTXR1 can act as a relatively low affinity pagA receptor in tissue culture model systems, it does not play a primary role in anthrax toxin induced effects in mouse models (Liu et al. 2009). While some studies suggest that ANTXR1 is associated with palmitoylated LRP6 (low density lipoprotein receptor related protein 6 - Abrami et al. 2008) in the plasma membrane and that the latter molecule can function as a co-receptor (Wei et al. 2006), the role of LRP6 in PA83 uptake remains uncertain (reviewed by van der Goot & Young 2009) and no function for LRP6 is annotated here.
Identifier: R-HSA-3769397
Species: Homo sapiens
Compartment: plasma membrane, extracellular region
SOST is a secreted antagonist of WNT signaling that acts by binding to LRP5/6 (Li et al, 2005; Semenov et al, 2005; Veverka et al, 2005). Binding of SOST requires the first two YWTD EGF repeats of LRP5/6 and appears to inhibit WNT signaling by preventing the formation of the LRP5/6:FZD receptor complex (Li et al, 2005; Semenov et al, 2005).
Identifier: R-HSA-1458875
Species: Homo sapiens
Compartment: plasma membrane, cytosol, extracellular region
The canonical WNT signaling pathway is initiated when WNT ligands bind to the 7 pass transmembrane receptor Frizzled (FZD) proteins (reviewed in Saito-Diaz et al, 2013). The single pass low-density lipoprotein receptor-related protein (LRP) 5/6 membrane proteins are thought to act as co-receptors with FZD proteins for WNTs, although the details are not fully worked out and a FZD:LRP interaction has not been demonstrated with endogenous proteins in vivo (reviewed in He et al, 2004). LRP5/6 have also been shown to bind directly to a subset of WNT proteins, although the data is conflicting (see for instance Tamai et al, 2000; Semenov et al, 2001; Cong et al, 2004; Wu and Nusse, 2002; Mao et al, 2001). Recent crystal structures have demonstrated direct binding of purified WNT proteins to LRP6 and FZD8 in vitro (Ahn et al, 2011; Janda et al, 2012; Chu et al, 2013), but it is not clear whether the LRP and FZD receptors bind WNTs independently, sequentially or cooperatively in vivo (reviewed in He et al, 2004; Saito-Diaz et al, 2013).
Identifier: R-HSA-201677
Species: Homo sapiens
Compartment: plasma membrane, cytosol, extracellular region
LRP5/6 contains 5 PPP(S/T)PxS motifs in its intracellular domain which have been shown to be phosphorylated by a membrane-associated pool of GSK3beta. Individual phosphorylation of each of these motifs promotes interaction with AXIN and stimulates WNT signaling as assessed by activation of a TCF/beta-catenin responsive reporter (Tamai et al, 2004; Zeng et al, 2005; MacDonald et al, 2008). In the context of full length LRP6, phosphorylation of the five motifs shows cooperative stimulation of AXIN binding and WNT signaling. GSK3beta-mediated phosphorylation of LRP6 is thought to prime the receptor for subsequent phosphorylation by CSNK1 (Zeng et al, 2005; reviewed in He et al, 2004).
Identifier: R-HSA-1504188
Species: Homo sapiens
Compartment: plasma membrane, cytosol
DVL is recruited to the plasma membrane through a direct interaction between its PDZ domain and a conserved motif of FZD located after the seventh transmembrane region. Recruitment of DVL to the receptor complex is thought to initiate recruitment of AXIN and GSK3beta (Fujii et al, 2007; Wong et al, 2003; Zeng et al, 2008; Tauriello et al, 2012).
Identifier: R-NUL-1458902
Species: Homo sapiens, Xenopus tropicalis
Compartment: plasma membrane, cytosol, extracellular region
Xenopus tropicalis Casein kinase 1 gamma was identified in a screen for proteins that covalently modify LRP6. CK1gamma was shown to phosphorylate LRP6 in vitro and in vivo. This phosphorylation is required for Axin recruitment and WNT signaling (Davidson et al, 2005).
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