| + |
CSNK1E | up-regulates 
phosphorylation
|
LRP6 |
0.263 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-145049 |
Ser1420 |
YVVHGPAsVPLGYVP |
Homo sapiens |
|
| pmid |
sentence |
| 16513652 |
We find that ckiepsilon binds to lrp5 and lrp6 in vitro and in vivo and identify three ckiepsilon-specific phosphorylation sites in lrp6. Two of the identified phosphorylation sites, ser1420 and ser1430, influence wnt signaling in vivo, |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-145053 |
Ser1430 |
LGYVPHPsSLSGSLP |
Homo sapiens |
|
| pmid |
sentence |
| 16513652 |
We find that ckiepsilon binds to lrp5 and lrp6 in vitro and in vivo and identify three ckiepsilon-specific phosphorylation sites in lrp6. Two of the identified phosphorylation sites, ser1420 and ser1430, influence wnt signaling in vivo, |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GSK3A | up-regulates activity
phosphorylation
|
LRP6 |
0.631 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275398 |
Ser1490 |
AILNPPPsPATERSH |
Homo sapiens |
|
| pmid |
sentence |
| 35487243 |
Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CyclinY/CDK14 | up-regulates activity
phosphorylation
|
LRP6 |
0.343 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273015 |
Ser1490 |
AILNPPPsPATERSH |
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 24794231 |
Compared with the wild-type CDK14, CDK14D256A mutant showed 2-fold reduced phosphorylation of LRP6 at Ser-1490, a known substrate of the CDK14/CCNY complex| It is also reported to be required for maximal phosphorylation of LRP6 on Ser 1490 and activation of Wnt signaling |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SIK2 | up-regulates activity
phosphorylation
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275399 |
Ser1490 |
AILNPPPsPATERSH |
Homo sapiens |
Breast Cancer Stem Cell |
| pmid |
sentence |
| 35277657 |
Mechanistically, SIK2, phosphorylated by CK1α, directly phosphorylated LRP6 in a SIK2 kinase activity-dependent manner, leading to Wnt/β-catenin signaling pathway activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275404 |
Ser1490 |
AILNPPPsPATERSH |
Homo sapiens |
Breast Cancer Stem Cell |
| pmid |
sentence |
| 35277657 |
Mechanistically, SIK2, phosphorylated by CK1α, directly phosphorylated LRP6 in a SIK2 kinase activity-dependent manner, leading to Wnt/β-catenin signaling pathway activation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GSK3B | up-regulates activity
phosphorylation
|
LRP6 |
0.793 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-143041 |
Ser1490 |
AILNPPPsPATERSH |
Homo sapiens |
|
| pmid |
sentence |
| 16341017 |
Glycogen synthase kinase 3 (gsk3), which is known for its inhibitory role in wnt through the promotion of beta-catenin phosphorylation and degradation, mediates the phosphorylation and activation of lrp6. We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT/FLT3 |
| + |
GSK3B/Axin/APC | up-regulates activity
phosphorylation
|
LRP6 |
0.732 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228014 |
Ser1490 |
AILNPPPsPATERSH |
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 16341017 |
Glycogen synthase kinase 3 (gsk3), which is known for its inhibitory role in wnt through the promotion of beta-catenin phosphorylation and degradation, mediates the phosphorylation and activation of lrp6. We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
CDK14 | up-regulates
phosphorylation
|
LRP6 |
0.334 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-162924 |
Ser1490 |
AILNPPPsPATERSH |
Homo sapiens |
|
| pmid |
sentence |
| 20059949 |
Low-density lipoprotein receptor related proteins 5 and 6 (lrp5/6) are transmembrane receptors that initiate wnt/beta-catenin signaling. Phosphorylation of pppsp motifs in the lrp6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide rnai screen, we show that pppsp phosphorylation requires the drosophila cyclin-dependent kinase (cdk) l63. L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CSNK1D | up-regulates activity
phosphorylation
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275402 |
Thr1479 |
SSSSTKGtYFPAILN |
Homo sapiens |
|
| pmid |
sentence |
| 35487243 |
Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275403 |
Thr1493 |
NPPPSPAtERSHYTM |
Homo sapiens |
|
| pmid |
sentence |
| 35487243 |
Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CSNK1G3 | up-regulates activity
phosphorylation
|
LRP6 |
0.289 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275400 |
Thr1479 |
SSSSTKGtYFPAILN |
Homo sapiens |
|
| pmid |
sentence |
| 35487243 |
Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275401 |
Thr1493 |
NPPPSPAtERSHYTM |
Homo sapiens |
|
| pmid |
sentence |
| 35487243 |
Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CSNK1G1 | up-regulates
phosphorylation
|
LRP6 |
0.543 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-143029 |
Thr1479 |
SSSSTKGtYFPAILN |
Homo sapiens |
|
| pmid |
sentence |
| 16341016 |
Ck1gamma is associated with lrp6, which has multiple, modular ck1 phosphorylation sites. Wnt treatment induces the rapid ck1gamma-mediated phosphorylation of these sites within lrp6 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CSNK1A1 | up-regulates
phosphorylation
|
LRP6 |
0.55 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-143034 |
Thr1493 |
NPPPSPAtERSHYTM |
Homo sapiens |
|
| pmid |
sentence |
| 16341017 |
We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin.Site ii, like site i, was phosphorylated, as detected by means of a phospho-specific antibody (ab1493, for phosphorylated t1493 in lrp6) |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-143037 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16341017 |
We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT/FLT3 |
| + |
PKA | up-regulates activity
phosphorylation
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275416 |
Thr1548 |
YAPSRRMtSVATAKG |
in vitro |
|
| pmid |
sentence |
| 21406690 |
PKA phosphorylated LRP6, which enhanced the binding of Gα(s) to LRP6, its localization to the plasma membrane, and the production of cAMP in response to PTH. Only alteration of Thr1548 abolished the phosphorylation of LRP6C by PKA (Fig. 6B), and mass spectrometry analysis confirmed that Thr1548 was the PKA phosphorylation site in LRP6C (fig. S1). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
WNT5A | up-regulates activity
binding
|
LRP6 |
0.757 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131841 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
LRP6 | down-regulates activity 
binding
|
GSK3B/Axin/APC |
0.732 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227942 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19107203 |
These observations demonstrate that phosphorylated lrp6/5 both recruits and directly inhibits gsk3beta using two distinct portions of its cytoplasmic sequence binding of wnts to the coreceptors frizzled and lrp6/5 leads to phosphorylation of pppspxs motifs in the lrp6/5 intracellular region and the inhibition of gsk3beta bound to the scaffold protein axin.These Observations demonstrate that phosphorylated lrp6/5 both recruits and directly inhibits gsk3beta using two distinct portions of its cytoplasmic sequence. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
KREMEN1 | up-regulates 
|
LRP6 |
0.64 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-88891 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12050670 |
Dkk1 has been shown to inhibit wnt signalling by binding to and antagonizing lrp5/6. Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to block wnt/beta-catenin signalling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MACF1 | up-regulates
|
LRP6 |
0.297 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-147457 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 16815997 |
Macf1 appeared to be involved in the translocation and subsequent binding of the axin complex to lrp6 at the cell membrane. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNT1 | up-regulates activity
binding
|
LRP6 |
0.827 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169648 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21078818 |
Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
CAPRIN2 | up-regulates
binding
|
LRP6 |
0.359 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-187177 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19619488 |
A cytoplasmic protein in vertebrates, referred to as caprin-2, binds to lrp6 and facilitates lrp6 phosphorylation by gsk3 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZNRF3 | down-regulates
ubiquitination
|
LRP6 |
0.655 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-199656 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23151663 |
Znrf3 is associated with the wnt receptor complex, and inhibits wnt by promoting the turnover of frizzled and lrp6. Frizzled receptors are regu__lated by cycles of ubiquitylation and deubiquitylation, and znrf3 and rnf43 act as frizzled ubiquitin ligases, removing frizzled and possibly lrp6 from the plasma membrane. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-197420 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22575959 |
Znrf3 is associated with the wnt receptor complex, and inhibits wnt by promoting the turnover of frizzled and lrp6. Frizzled receptors are regu__lated by cycles of ubiquitylation and deubiquitylation, and znrf3 and rnf43 act as frizzled ubiquitin ligases, removing frizzled and possibly lrp6 from the plasma membrane. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
WNT16 | up-regulates
binding
|
LRP6 |
0.541 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131677 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRP6 | form complex 
binding
|
LPR5/6 |
0.403 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256175 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27821587 |
Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are co-receptors for Wnt ligands. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNT9B | up-regulates
binding
|
LRP6 |
0.617 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-163552 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20093360 |
We find that wnt9b binds to a different part of the lrp6 extracellular domain |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRP6 | down-regulates activity
relocalization
|
AXIN1 |
0.835 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-148668 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16890161 |
The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179469 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18632848 |
The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104493 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12897152 |
The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
FZD2 | up-regulates activity
binding
|
LRP6 |
0.666 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258965 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18077588 |
Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FZD5 | up-regulates activity
binding
|
LRP6 |
0.737 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258966 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18077588 |
Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DVL2 | up-regulates activity
binding
|
LRP6 |
0.689 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66362 |
|
|
Homo sapiens |
L-929 Cell |
| pmid |
sentence |
| 10196136 |
Dvl is required for lrp6 phosphorylation, which is essential for subsequent steps of signal transduction. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNT2 | up-regulates
binding
|
LRP6 |
0.672 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131730 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DVL1 | up-regulates activity
binding
|
LRP6 |
0.706 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-156072 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17569865 |
The scaffold protein dishevelled (dvl) is required for lrp6 phosphorylation and aggregation. We propose that wnts induce coclustering of receptors and dvl in lrp6-signalosomes, which in turn triggers lrp6 phosphorylation to promote axin recruitment and beta-catenin stabilization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis |
| + |
WNT7A | up-regulates activity
binding
|
LRP6 |
0.647 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131903 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
PTH1R | up-regulates
binding
|
LRP6 |
0.338 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-199533 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23151663 |
Parathyroid hormone (pth) binding to its receptor pth1r induces association of the pthpth1r complex with lrp6and phosphorylation of pppsp sites by protein kinase_ a, which in turn triggers wnt. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNT3 | up-regulates
binding
|
LRP6 |
0.648 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131823 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNT3A | up-regulates activity
binding
|
LRP6 |
0.789 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131829 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins are a large family of secreted glycoproteins. Wnt proteins bind to the Frizzled receptors and LRP5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169660 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21078818 |
Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.All the frizzled genes studied have |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-148671 |
|
|
Homo sapiens |
HeLa-S3 Cell |
| pmid |
sentence |
| 16890161 |
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. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
MAPK1 | up-regulates
phosphorylation
|
LRP6 |
0.302 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169001 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20974802 |
We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Wnt | up-regulates activity
binding
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131577 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis |
| + |
WNT4 | up-regulates
binding
|
LRP6 |
0.647 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131835 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNT9A | up-regulates
binding
|
LRP6 |
0.638 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-132076 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ERK1/2 | up-regulates
phosphorylation
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244662 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20974802 |
We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT/FLT3 |
| + |
WNT10B | up-regulates activity
binding
|
LRP6 |
0.609 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131631 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MEST | down-regulates activity 
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255826 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21375506 |
Mest/Peg1 inhibited maturation of LRP6 by controlling the glycosylation of LRP6. Knockdown of Mest/Peg1, which might enhance Wnt signalling, blocked adipogenic differentiation of 3T3-L1 cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRP6 | up-regulates activity
binding
|
DVL1 |
0.706 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262526 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23209147 |
The Wnt–FZD–LRP5/6 trimeric complex recruits Dishevelled (DVL) and Axin through the intracellular domains of FZD and LRP5/6, resulting in inhibition of β-catenin phosphorylation and thus ensuing β-catenin stabilization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis |
| + |
KREMEN2 | down-regulates
binding
|
LRP6 |
0.638 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-88894 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12050670 |
Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to block wnt/beta-catenin signalling. Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of the wnt receptor lrp6 from the plasma membrane. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK14 | up-regulates activity
|
LRP6 |
0.334 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273019 |
|
|
|
|
| pmid |
sentence |
| 24794231 |
Compared with the wild-type CDK14, CDK14D256A mutant showed 2-fold reduced phosphorylation of LRP6 at Ser-1490, a known substrate of the CDK14/CCNY complex| It is also reported to be required for maximal phosphorylation of LRP6 on Ser 1490 and activation of Wnt signaling |
|
| Publications: |
1 |
| + |
CAV1 | up-regulates
binding
|
LRP6 |
0.675 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-148665 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16890161 |
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. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNT5B | up-regulates
binding
|
LRP6 |
0.625 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131888 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Gbeta | up-regulates
phosphorylation
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270024 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20974802 |
We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCN2 | up-regulates
binding
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178875 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18528331 |
Igfbp-4 physically interacted with a wnt receptor, frizzled 8 (frz8), and a wnt co-receptor, low-density lipoprotein receptor-related protein 6 (lrp6), and inhibited the binding of wnt3a to frz8 and lrp6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
has-mir-126-3p | down-regulates quantity by repression
post transcriptional regulation
|
LRP6 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278836 |
|
|
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 25240815 |
These results provided strong evidence that LRP6 is a target of miR-126-3p in HCC and mediates the metastasis function of miR-126-3p in HCC. | MiR-126-3p inhibits HCC metastasis by directly targeting LRP6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
hsa-miR-513c-5p | down-regulates quantity by repression
post transcriptional regulation
|
LRP6 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278838 |
|
|
Homo sapiens |
SNB-19 Cell |
| pmid |
sentence |
| 26063413 |
A luciferase reporter assay demonstrated that the downregulation of LRP6 was mediated by miR‑513c through the LRP6 3'‑UTR. These results demonstrated that LRP6 is a bona fide target of miR‑513c.| LRP6 is a direct target of miRNA‑513c. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
hsa-miR-610 | down-regulates quantity by repression
post transcriptional regulation
|
LRP6 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278839 |
|
|
Homo sapiens |
BEL-7404 Cell |
| pmid |
sentence |
| 25491321 |
Results indicate that miR-610 negatively regulated these proteins via directly binding to their 3’UTRs. These data further confirm that miR-610 suppresses HCC cell tumorigenicity by inhibiting the activity of β-catenin via targeting LRP6 and TBL1X. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
hsa-miR-183-5p | down-regulates quantity by repression
post transcriptional regulation
|
LRP6 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278842 |
|
|
Homo sapiens |
MG-63 Cell |
| pmid |
sentence |
| 29402412 |
Taken together, these data indicate that miR-183 down-regulates LRP6 expression by directly targeting its 3'-UTR. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DAB2 | down-regulates
binding
|
LRP6 |
0.497 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-196925 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22491013 |
Wnt stimulation induces the casein kinase 2 (ck2)-dependent phosphorylation of lrp6 at s1579, promoting its binding to dab2 and internalization with clathrin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRP6 | down-regulates quantity by destabilization
relocalization
|
GSK3B/Axin/APC |
0.732 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227939 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18632848 |
The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
WNT10A | up-regulates
binding
|
LRP6 |
0.56 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131622 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRP6 | up-regulates activity
|
GSK3B |
0.793 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255484 |
|
|
|
|
| pmid |
sentence |
| 15229249 |
We speculate that DKK1 produced by βAP-treated neurons suppresses the canonical Wnt signaling pathway by interacting with LRP5/6 and therefore facilitates GSK3β activation. |
|
| Publications: |
1 |
| Pathways: | WNT/FLT3 |
| + |
WNT11 | up-regulates activity
binding
|
LRP6 |
0.571 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-131637 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
CSNK1A1L | up-regulates
phosphorylation
|
LRP6 |
0.255 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-184699 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19293931 |
Ck1 also phosphorylates lrp6 at the second ser residue in the pppspxs motif ck1_ in the lrp5/e-cadherin/p120-catenin complex temporally coincides with p120-catenin phosphorylation in ser268. moreover, and considering the close similarity between the catalytic domains of ck1_ and ck1_, it is possible that ck1_ is indeed responsible for the phosphorylation at ser1420 and ser1430 in lrp5/6 that negatively affects wnt signaling by still not defined mechanisms |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-173853 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21606194 |
Ck1 also phosphorylates lrp6 at the second ser residue in the pppspxs motif ck1_ in the lrp5/e-cadherin/p120-catenin complex temporally coincides with p120-catenin phosphorylation in ser268. moreover, and considering the close similarity between the catalytic domains of ck1_ and ck1_, it is possible that ck1_ is indeed responsible for the phosphorylation at ser1420 and ser1430 in lrp5/6 that negatively affects wnt signaling by still not defined mechanisms |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GRK5 | up-regulates
phosphorylation
|
LRP6 |
0.546 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-23330 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 2787365 |
we found that g protein-coupled receptor kinases 5 and 6 (grk5/6), traditionally known to phosphorylate and desensitize 7tm g protein-coupled receptors, directly phosphorylate the pppsp motifs on single transmembrane lrp6 and regulate wnt/lrp6 signaling |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKACA | up-regulates activity
phosphorylation
|
LRP6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-181979 |
|
|
Rattus norvegicus |
Osteoblast |
| pmid |
sentence |
| 18981475 |
These results suggest that camppka activation is involved in activation of lrp6(...) our results demonstrate that lrp6 can be directly phosphorylated by pka catalytic subunit. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| Pathways: | WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis |
| + |
PIPP | up-regulates
|
LRP6 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-180797 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18772438 |
Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates [ptdins (4,5)p2] through frizzled and dishevelled, the latter of which directly interacted with and activated pip5ki. In turn, ptdins (4,5)p2 regulated phosphorylation of lrp6 at thr1479 and ser1490 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DKK1 | down-regulates
binding
|
LRP6 |
0.905 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109247 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11448771 |
We report that dkk-1 is a high-affinity ligand for lrp6 and inhibits wnt signaling by preventing fz-lrp6 complex formation induced by wnt. Dkk1 has been shown to inhibit wnt by binding to and antagonizing lrp5/6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT/FLT3 |
| + |
MAPK8 | up-regulates
phosphorylation
|
LRP6 |
0.384 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169007 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20974802 |
We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis |
| + |
WNT8B | up-regulates
binding
|
LRP6 |
0.615 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-132027 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15578921 |
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AMER1 | up-regulates activity
binding
|
LRP6 |
0.475 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-24265 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21304492 |
Knockdown of Amer1 reduces Wnt-induced LRP6 phosphorylation, Axin translocation to the plasma membrane and formation of LRP6 signalosomesThe generation of PtdIns(4,5)P2 in regions of receptor activity triggers the recruitment of Amer1 proteins, which in turn promote LRP6 phosphorylation by recruiting Axin/GSK3_ and CK1gamma to LRP6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZNRF3 | down-regulates quantity
ubiquitination
|
LRP6 |
0.655 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260112 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22575959 |
Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK3 | up-regulates
phosphorylation
|
LRP6 |
0.314 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169004 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20974802 |
We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
hsa-miR-202-5p | down-regulates quantity by repression
post transcriptional regulation
|
LRP6 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278841 |
|
|
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 24704686 |
Taken together, our results suggested that LRP6 mRNA is a direct target of miR-202 in HCC cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FZD8 | up-regulates activity
binding
|
LRP6 |
0.754 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169638 |
|
|
Homo sapiens |
SAOS-2 Cell |
| pmid |
sentence |
| 21078818 |
Ligands such as Wnt1, Wnt3a, and Wnt8 couple the seven-transmembrane domain receptor Frizzled (Fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (LRP5/6) to activate WntBeta-catenin signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PIP5K1A | up-regulates
|
LRP6 |
0.273 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-180800 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18772438 |
Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates [ptdins (4,5)p2] through frizzled and dishevelled, the latter of which directly interacted with and activated pip5ki. In turn, ptdins (4,5)p2 regulated phosphorylation of lrp6 at thr1479 and ser1490 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FZD4 | up-regulates activity
binding
|
LRP6 |
0.648 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258964 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18077588 |
Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDH1 | up-regulates
binding
|
LRP6 |
0.364 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168464 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20940130 |
P12Beta-catenin_ also associates to the_ wnt_ co-receptor lrp5/6, an interaction mediated by e-cadherin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
LRP6
- 
- 