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CTNNB1 — LRP6
Pathways - manually collected, often from reviews:
-
NCI Pathway Database Canonical Wnt signaling pathway:
beta catenin (CTNNB1)
→
WNT3A/LRP6/FZD5 complex (WNT3A-LRP6-FZD5)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
beta catenin (CTNNB1)
→
WNT3A/LRP6/FZD5/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-AXIN1-GSK3B_GSK3A)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1)
→
WNT3A/LRP6/FZD5 complex (WNT3A-LRP6-FZD5)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1)
→
WNT3A/LRP6/FZD5/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-AXIN1-GSK3B_GSK3A)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Degradation of beta catenin:
WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2)
→
Axin1/APC//beta catenin complex (AXIN1-APC-CTNNB1)
(modification, inhibits)
Kishida et al., Oncogene 1999, Kodama et al., J Biol Chem 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Orford et al., J Biol Chem 1997, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Degradation of beta catenin:
WNT3A/LRP6/FZD5 complex (WNT3A-LRP6-FZD5)
→
Axin1/APC//beta catenin complex (AXIN1-APC-CTNNB1)
(modification, inhibits)
Kishida et al., Oncogene 1999, Kodama et al., J Biol Chem 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Orford et al., J Biol Chem 1997, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Canonical Wnt signaling pathway:
beta catenin (CTNNB1)
→
WNT3A/LRP6/FZD5/DVL/Axin1/GSK3/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
beta catenin (CTNNB1)
→
WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1)
→
WNT3A/LRP6/FZD5/DVL/Axin1/GSK3/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1)
→
WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2)
→
beta catenin (CTNNB1)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2)
→
Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
beta catenin (CTNNB1)
→
WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
-
NCI Pathway Database Canonical Wnt signaling pathway:
Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1)
→
WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A)
(modification, collaborate)
Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
Evidence: mutant phenotype
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Mao et al., Nature 2001
:
Dkk1 blocks
LRP6 mediated
Wnt/beta-catenin signalling by interacting with domains that are distinct from those required for Wnt/Frizzled interaction
Semënov et al., Curr Biol 2001
:
Our findings suggest that
Wnt-Fz-LRP6 complex formation, but not Wnt-Fz interaction,
triggers Wnt/beta-catenin signaling
Cong et al., Development 2004
:
In addition, the
beta-catenin signaling
mediated by ectopic expression of
LRP is not dependent on Disheveled or Wnt, but can also be augmented by oligomerization of LRP receptors
Swiatek et al., J Biol Chem 2006
:
Two of the identified phosphorylation sites, Ser1420 and Ser1430, influence Wnt signaling in vivo, since
LRP6 with mutation of these sites is a more potent
activator of both
beta-catenin accumulation and Lef-1 reporter activity
Mukhopadhyay et al., Development 2006
:
The Dkk family of secreted cysteine-rich proteins
regulates Wnt/beta-catenin signaling by interacting with the Wnt co-receptor
Lrp5/6
Yamamoto et al., Dev Cell 2006
:
Here, we present evidence that
LRP6 is internalized with caveolin and that the components of this endocytic pathway are
required not only for Wnt-3a induced internalization of LRP6 but also for accumulation of
beta-catenin ... Overall, our data suggest that Wnt-3a triggers the interaction of
LRP6 with caveolin and promotes recruitment of Axin to LRP6 phosphorylated by glycogen synthase kinase-3beta and that caveolin thereby
inhibits the binding of
beta-catenin to Axin
Kofron et al., Development 2007
:
Wnt11/beta-catenin signaling in both oocytes and early embryos
acts through
LRP6 mediated regulation of axin ... In the oocyte, Wnt11 and/or LRP6 regulates axin to maintain beta-catenin at a low level, while in the embryo, asymmetrical
Wnt11/LRP6 signaling
stabilizes beta-catenin and enriches it on the dorsal side
Bhat et al., Gene 2007
:
In the presence of Wnt1,
LRP5 or the HBM variant ( LRP5-G171V )
induces beta-catenin nuclear translocation and activates T cell factor ( TCF ) -luciferase reporter activity
Tahinci et al., Development 2007
:
We propose a model in which
Lrp6 plays a critical role in the switch from Wnt/PCP to
Wnt/beta-catenin signaling
Zeng et al., Development 2008
:
We demonstrated previously that Wnt induced
Lrp6 phosphorylation via glycogen synthase kinase 3 ( Gsk3 )
initiates Wnt/beta-catenin signaling
Cselenyi et al., Proc Natl Acad Sci U S A 2008
:
Using an Axin mutant that does not degrade in response to LRP6, we demonstrate that
LRP6 can
stabilize beta-catenin in the absence of Axin turnover ... Through experiments in egg extract and reconstitution with purified proteins, we identify a mechanism whereby
LRP6 stabilizes
beta-catenin independently of Axin degradation by directly inhibiting GSK3 's phosphorylation of beta-catenin
Yamamoto et al., Dev Cell 2008
:
The phosphorylation and internalization of
LRP6 occurred independently of one another, and both were
necessary for the accumulation of
beta-catenin ... These results indicate that Wnt3a and Dkk1 shunt
LRP6 to distinct internalization pathways in order to activate and
inhibit the
beta-catenin signaling, respectively
Beagle et al., J Cell Biochem 2009
:
LRP6-ICD and a mutant in which all 5 PPP ( S/T ) P motifs were changed to PPP ( A ) P motifs equivalently interacted with and attenuated GSK3beta activity in vitro, and both constructs
inhibited the in situ GSK3beta mediated phosphorylation of
beta-catenin and tau to the same extent
Lu et al., Biochemistry 2010
:
Mesd not only blocks binding of Wnt antagonists Dkk1 and Sclerostin to LRP5 and
LRP6 but also
inhibits Wnt3A and Rspondin1 induced
Wnt/beta-catenin signaling in LRP5- and LRP6 expressing cells