Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 Phosphorylation

By J. Bilić, Ya-Lin Huang, G. Davidson, T. Zimmermann, Cristina Cruciat, M. Bienz, Christof Niehrs. Science, 2007

919 citations recorded by the source corpus.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bae474a92dfa26526a59e5927e055e6ded8fa408

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. R. Nusse

In Molecular Biology

1. Hans Clevers
2. R. Nusse
3. T. Valenta
4. Konrad Basler
5. G. Hausmann
6. G. Schulte
7. J. Petersen
8. J. Dijksterhuis

Citations in the corpus

• Towards an integrated view of Wnt signaling in development (2009, background): “In fact, the phosphorylation of LRP/Arrow, as well as its ability to form large aggregates or ‘signalosomes’, both of which require Frizzled function, have recently been shown to be indispensable for the accumulation of β-catenin upon Wnt stimulation in many species (Bilic et al., 2007; Tamai et al.”
• Wnt Signaling Requires the Sequestration of Glycogen Synthase Kinase 3 inside Multivesicular Endosomes (2010, positive): “Designated as LRP6-signalosomes, these aggregates are very prominent in cells in which the Wnt pathway is activated by CA-LRP6, Dvl, or DIX-Ctail overexpression (Bilic et al., 2007, Metcalfe et al., 2010).”
• R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling (2011, background): “Wnt/β-catenin signaling is characterized by a series of events starting with phosphorylation and internalization of LRP5/6 subsequent to ligand binding, followed by inhibition of GSK3β and an increase in the levels of active β-catenin (28).”
• β-Catenin hits chromatin: regulation of Wnt target gene activation (2009, background): “When Wnt binds to the seven transmembrane domain receptors frizzled and the low density lipoprotein receptor-related protein 5 ( LRP5 ) or LRP6 co-receptors, the cytoplasmic protein dishevelled ( DVL ) is recruited to the receptor complex, and this is suggested to cause sequestration of the rate-l”
• Interplay of cadherin-mediated cell adhesion and canonical Wnt signaling. (2010, neutral): “2B) (Davidson et al. 2005; Bilic et al. 2007; Schwarz-Romond et al. 2007).”
• The many faces and functions of β‐catenin (2012, positive): “Ligand activated Frizzled receptors recruit the cytoplasmic protein Dishevelled (Dvl) to the receptor complex through direct binding; Dvl subsequently multimerizes and induces formation of so-called LRP-associated Wnt signalosomes (Bilic et al , 2007).”
• INTERNATIONAL UNION OF BASIC AND CLINICAL PHARMACOLOGY REVIEW WNT/Frizzled signalling: receptor-ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3 (2014, positive): “The formation of a WNT-FZD-LRP5/6 complex and the recruitment of the scaffolding protein Dishevelled (DVL) leads to the co-clustering of these proteins in signalosomes, which in turn triggers LRP6 phosphorylation (Bilic et al., 2007).”
• Osteocytes, mechanosensing and Wnt signaling. (2008, background): “Binding of Wnt to Lrp5 and frizzled, in addition to Dsh activation, also results in the phosphorylation of the cytoplasmic tail of Lrp5, likely mediated by Casein kinase 1γ (CK-1γ) (29), the binding of FRAT-1 to this tail and ultimately its association with axin.”
• Wnt signalling and its impact on development and cancer (2008, background): “(and possibly other protein kinases yet to be identified), and Dishevelled is recruited to the plasma membrane, where it interacts with Frizzled receptors and polymerizes with other Dishevelled molecule”
• The β-catenin destruction complex. (2013, background): “Activation of the coreceptors LRP5/6 and Fzd results in recruitment of the destruction complex to the membrane and formation of membrane-associated puncta associated with b-catenin activation (Cliffe et al. 2003; Tolwinski et al. 2003; Bilic et al. 2007; Schwarz-Romond et al. 2007b; Hendriksen et al”
• Targeting the Wnt/β-catenin signaling pathway in cancer (2020, background): “In the presence of Wnt ligand, the binding of Wnt ligand and receptors on the cell surface induces disheveled (DVL), causing the aggregation of the complex (AXIN, GSK3β, CK1, APC) to the receptor [15].”