Reactome: A Curated Pathway Database
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Pathways (14) Reactions (15) Proteins (2) Others (19)
Pathway: misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling (Homo sapiens)
LRP5 is subject to an in-frame missplicing event in breast and parathyroid cancers that renders the protein insensitive to inhibition by the WNT antagonist DKK1. Expression of the mutant protein results in elevated levels of active, unphosphorylated beta-catenin and enhanced TCF-dependent WNT-signaling, promoting cellular proliferation (Bjorklund et al 2007a, b; Bjorklund et al, 2009)
Last changed: 2015-02-09 16:16:33

Protein: UniProt:O75197 LRP5 (Homo sapiens)
Last changed: 2015-03-10 08:59:22

Pathway: Disease (Homo sapiens)
Biological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular viewpoint, human disease pathways have three mechanistic causes: the inclusion of microbially-expressed proteins, altered functions of human proteins, or changed expression levels of otherwise functionally
Last changed: 2015-03-06 23:15:47

Pathway: Signal Transduction (Homo sapiens)
Signal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such as hormones and growth factors, or reacting to other types of stimuli, such as light. Stimulation of transmembrane receptors leads to their conformational change which propagates the signal to the intracellu
Last changed: 2015-03-06 23:15:47

Pathway: Developmental Biology (Homo sapiens)
As a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are aspects of the roles of cell adhesion molecules in axonal guidance and myogenesis, of transcriptional regulation in hematopoiesis (specifically, B lymphopoiesis), pancreatic beta cell and whit
Last changed: 2015-03-06 23:15:47

Pathway: Signaling by Wnt (Homo sapiens)
WNT signaling pathways control a wide range of developmental and adult process in metozoans includin ... Frizzled (FZD) receptors in conjunction with the LRP5/6 co-receptors to activate a transcriptional cascade that controls processes such as cell fate, proliferation and self-renenwal of stem cells. Engagement of the FZD-LRP receptor by WNT ligand results in the stabilization and translocation of cy ...
Last changed: 2015-03-06 18:40:03

Reaction: phosphorylation of LRP5/6 cytoplasmic domain by membrane-associated GSK3beta (Homo sapiens)
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 conte
Last changed: 2015-03-06 18:40:03

Reaction: SOST binds LRP5/6 (Homo sapiens)
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)
Last changed: 2015-03-06 05:19:08

Reaction: DKK and KRM bind LRP5/6 (Homo sapiens)
DKK1, 2 and 4 are secreted antagonists of WNT signaling that act by binding to LRP5/6 and preventing the formation of an LRP:FZD receptor complex (Semenov et al, 2001; Mao et al, 2001; Bafico et al, 2001; reviewed in Niehrs, 2006). LRP6 has multiple independent WNT binding sites on its surface that are bound by different subsets of WNT proteins (Bourhis et al, 2010; Bourhis et al, 2011). Structural s
Last changed: 2015-03-06 07:18:40

Reaction: phosphorylation of LRP5/6 cytoplasmic domain by CSNKI (Homo sapiens)
After being phosphorylated by GSK3beta on the PPPSP motifs, LRP6 (and by extension LRP5) is phosphorylated at up to 5 sites by a member of the CSNK1 family (Davidson et al, 2005). One screen identified CSNK1gamma as a candidate kinase, while another study showed that CSNK1alpha, delta and epsilon contribute to this phosphorylation step (Davidson et al, 2005; Zeng et al, 2005). This sequential phospho
Last changed: 2015-03-06 18:40:03

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