| + |
GSK3B/Axin/APC | up-regulates activity 
phosphorylation
|
LRP6 |
0.737 |
| 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 |
| + |
GSK3B/Axin/APC | down-regulates activity 
phosphorylation
|
CTNNB1 |
0.896 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227870 |
Ser33 |
QQQSYLDsGIHSGAT |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19303846 |
GSK3β regulates β-catenin stability by phosphorylating serine and threonine residues (Ser33/37 and Thr41) important for targeting β-catenin for ubiquitin-dependent proteasomal degradation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227897 |
Ser33 |
QQQSYLDsGIHSGAT |
Homo sapiens |
|
| pmid |
sentence |
| 11955436 |
Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227885 |
Ser33 |
QQQSYLDsGIHSGAT |
Homo sapiens |
|
| pmid |
sentence |
| 16293724 |
This leads to the inactivation and release of glycogen synthase kinase 3beta from its complex with axin, thereby relieving the inhibitory phosphorylation of beta-catenin and activating its signaling pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227874 |
Ser37 |
YLDSGIHsGATTTAP |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19303846 |
GSK3β regulates β-catenin stability by phosphorylating serine and threonine residues (Ser33/37 and Thr41) important for targeting β-catenin for ubiquitin-dependent proteasomal degradation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227889 |
Ser37 |
YLDSGIHsGATTTAP |
Homo sapiens |
|
| pmid |
sentence |
| 16293724 |
This leads to the inactivation and release of glycogen synthase kinase 3beta from its complex with axin, thereby relieving the inhibitory phosphorylation of beta-catenin and activating its signaling pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227901 |
Ser37 |
YLDSGIHsGATTTAP |
Homo sapiens |
|
| pmid |
sentence |
| 11955436 |
Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260015 |
Thr41 |
GIHSGATtTAPSLSG |
in vitro |
|
| pmid |
sentence |
| 11955436 |
β-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC) |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227866 |
Thr41 |
GIHSGATtTAPSLSG |
Homo sapiens |
|
| pmid |
sentence |
| 23151663 |
Beta-catenin phosphorylation in vivo is sequentially carried out by two distinct kinases, ckialfa and gsk-3. Ckialfa phosphorylation of s45 proceeds and is required for subsequent gsk-3 phosphorylation of t41, s37, and s33 one key substrate of gsk3 is the transcriptional co-activator beta catenin, whichis inactivated by gsk3 mediated phosphorylation and targeted for proteasomal degradation in unstimulated cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227905 |
Thr41 |
GIHSGATtTAPSLSG |
Homo sapiens |
|
| pmid |
sentence |
| 11955436 |
Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227878 |
Thr41 |
GIHSGATtTAPSLSG |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19303846 |
GSK3β regulates β-catenin stability by phosphorylating serine and threonine residues (Ser33/37 and Thr41) important for targeting β-catenin for ubiquitin-dependent proteasomal degradation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227893 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16293724 |
Because phosphorylation of β-catenin by GSK-3β leads to its rapid ubiquitination and subsequent degradation in the proteosome, inactivation of GSK-3β is often a prerequisite for stimulating the accumulation, nuclear translocation, and functional activity of β-catenin |
|
| Publications: |
11 |
Organism: |
Homo Sapiens, In Vitro |
| Tissue: |
Brain, Colonic Cancer Cell |
| Pathways: | Colorectal Carcinoma, Hepatocellular Tumor, Wnt in cancer, WNT Signaling, WNT Signaling and Myogenesis |
| + |
GSK3B/Axin/APC | down-regulates activity
phosphorylation
|
PSEN1 |
0.394 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228018 |
Ser353 |
SHLGPHRsTPESRAA |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17360711 |
We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228022 |
Ser357 |
PHRSTPEsRAAVQEL |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17360711 |
We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GSK3B/Axin/APC | down-regulates activity
phosphorylation
|
ROR2 |
0.331 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228026 |
Ser864 |
PKPSSHHsGSGSTST |
Homo sapiens |
|
| pmid |
sentence |
| 21078818 |
We identify ror2 ser 864 as a critical residue phosphorylated by gsk3 and required for noncanonical receptor activation by wnt5a, analogous to the priming phosphorylation of low-density receptor-related protein 6 (lrp6) in response to wnt3a. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK3 | down-regulates activity
phosphorylation
|
GSK3B/Axin/APC |
0.348 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262520 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 28646232 |
We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
AURKA | down-regulates activity
phosphorylation
|
GSK3B/Axin/APC |
0.354 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227923 |
|
|
Homo sapiens |
MKN-45 Cell |
| pmid |
sentence |
| 19060929 |
The recombinant human aurka protein phosphorylated the gsk-3beta protein at ser 9 in a concentration-dependent manner, in vitro. The phosphorylation of beta-catenin (ser33/37/thr41) by gsk-3beta is known to target beta-catenin towards degradation. In line with our findings, the increase in phospho-gsk-3beta level was accompanied by a significant decrease in beta-catenin phosphorylation (ser33/37/thr41) and accumulation of beta-catenin protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CSNK1D | up-regulates
binding, phosphorylation
|
GSK3B/Axin/APC |
0.542 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227973 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12000790 |
We conclude that a major role of axin in the wnt is to provide the kinase activity that initiates the beta-catenin phosphorylation cascade at s45. This process is mediated by cki, the alfa, delta, or epsilon isoform, all detected in association with axin by lc/ms. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227970 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12000790 |
We conclude that a major role of axin in the wnt is to provide the kinase activity that initiates the betBeta-catenin phosphorylation cascade at s45 . This process is mediated by cki, the alfa, delta, or ? Isoform, all detected in association with axin by lc/mscomplex of axin and casein kinase i (cki) induces betBeta-catenin phosphorylation at a single site: serine 45 (s45) |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
MAPK1 | down-regulates activity
phosphorylation
|
GSK3B/Axin/APC |
0.319 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262521 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 28646232 |
We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
GNAS | up-regulates
binding
|
GSK3B/Axin/APC |
0.378 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227988 |
|
|
Homo sapiens |
Colonic Cancer Cell |
| pmid |
sentence |
| 16293724 |
We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein) coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
WNT5A | down-regulates activity 
|
GSK3B/Axin/APC |
0.424 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227961 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21078818 |
We demonstrate here that prototype canonical wnt3a and noncanonical wnt5a ligands specifically trigger completely unrelated endogenous coreceptors-lrp5/6 and ror1/2, respectively-through a common mechanism that involves their wnt-dependent coupling to the frizzled (fzd) coreceptor and recruitment of shared components, including dishevelled (dvl), axin, and glycogen synthase kinase 3 (gsk3) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
FRAT1 | up-regulates
binding
|
GSK3B/Axin/APC |
0.646 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227994 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9635432 |
The frat family consists of three members: frat-1, -2, and -3. It has been shown that different sites of frat-1 interact with gsk-3 and dvl-1 and that wnt-1 disintegrates the complex formation of frat-1, dvl-1, and axin, resulting in the activation of the wnt signaling pathway |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MACF1 | down-regulates activity
|
GSK3B/Axin/APC |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228000 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 16815997 |
In the absence of wnt, macf1 associated with a complex that contained axin, betBeta-catenin, gsk3beta, and apc. Upon wnt stimulation, macf1 appeared to be involved in the translocation and subsequent binding of the axin complex to lrp6 at the cell membrane. Macf1 is involved in the translocation of the complex containing axin, Beta-catenin, and gsk3_ but not apc from the cytosol to the cell membrane, where axin and macf1 bind to lrp-5/6. Subsequently, gsk3_ is inactivated by phosphorylation, axin is degraded, and Beta-catenin is released and enters the nucleus, where it can activate the wnt-responsive genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRP5 | down-regulates quantity by destabilization
relocalization
|
GSK3B/Axin/APC |
0.69 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227930 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11336703 |
Lrp-5, a close homolog of lrp-6 (hey et al., 1998), functions as a coreceptor for wnt proteins in mammalian cells and that it can transduce the canonical wnt signals, at least in part by binding and recruiting axin to membranes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Colorectal Carcinoma, WNT Signaling, WNT Signaling and Myogenesis |
| + |
DVL1 | down-regulates activity
binding
|
GSK3B/Axin/APC |
0.716 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227917 |
|
|
Chlorocebus aethiops |
COS Cell |
| pmid |
sentence |
| 10196136 |
We have recently found that Dvl-1 directly binds to Axin and that the binding of Dvl-1 to Axin does not affect the interaction of GSK-3beta with Axin. It is possible that the binding of Dvl to Axin induces the structural change of the Axin complex; therefore GSK-3beta does not effectively phosphorylate Axin. This is the first demostration showing that Dvl inhibits the function of GSK-3beta directly. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227911 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20837657 |
In canonical wnt signaling, dsh phosphorylation inhibits the apcaxingsk3 complex, leading to beta-catenin stabilization. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227914 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20837657 |
In canonical wnt signaling, dsh phosphorylation inhibits the apcaxingsk3 complex, leading to beta-catenin stabilization. |
|
| Publications: |
3 |
Organism: |
Chlorocebus Aethiops, Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Wnt in cancer, WNT Signaling, WNT Signaling and Myogenesis |
| + |
TNKS | down-regulates quantity by destabilization
|
GSK3B/Axin/APC |
0.52 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261249 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 19759537 |
Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DVL2 | up-regulates
binding
|
GSK3B/Axin/APC |
0.656 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227920 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17529994 |
Dishevelled (dvl) transduces the wnt signal by interacting with the cytoplasmic axin complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAP4K5 | down-regulates activity
phosphorylation
|
GSK3B/Axin/APC |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228006 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16914735 |
Gckr can phosphorylate an n-terminal recombinant fusion protein of gsk3beta and enhance the in vivo phosphorylation of gsk3beta on serine 9reduction of gckr expression inhibits wnt3a-induced phosphorylation of gsk3beta at serine 9 and decreases the accumulation of cytosolic _-catenin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDC14B | up-regulates
dephosphorylation
|
GSK3B/Axin/APC |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227927 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18662541 |
The phosphatase cdc14b translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase apc/ccdh1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CSNK1A1 | up-regulates activity
binding
|
GSK3B/Axin/APC |
0.675 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227964 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19293931 |
In the absence of secreted wnt ligands, cytosolic beta-catenin is phosphorylated at ser45 by the priming kinase casein kinase 1 (ck1). Consequently, glycogen synthase kinase 3 (gsk3), in complex with axin and adenomatous polyposis coli (apc), phosphorylates beta-catenin at thr41, ser37, and ser33 apc cooperates with axin to promote the phosphorylation of b-catenin by gsk3 [which requires priming phosphorylation by casein kinase 1, alpha-isoform (ck1alpha)] |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227967 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22083140 |
In the absence of secreted wnt ligands, cytosolic beta-catenin is phosphorylated at ser45 by the priming kinase casein kinase 1 (ck1). Consequently, glycogen synthase kinase 3 (gsk3), in complex with axin and adenomatous polyposis coli (apc), phosphorylates beta-catenin at thr41, ser37, and ser33 apc cooperates with axin to promote the phosphorylation of b-catenin by gsk3 [which requires priming phosphorylation by casein kinase 1, alpha-isoform (ck1alpha)] |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Wnt in cancer, WNT Signaling |
| + |
GSK3B | form complex 
binding
|
GSK3B/Axin/APC |
0.84 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227299 |
|
|
Homo sapiens |
Colonic Cancer Cell |
| pmid |
sentence |
| 9734785 |
Axin, an inhibitor of the wnt pathway, interacts with beta-catenin, gsk-3beta and apc and reduces the beta-catenin level. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNT5A | down-regulates
|
GSK3B/Axin/APC |
0.424 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227958 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21078818 |
We demonstrate here that prototype canonical wnt3a and noncanonical wnt5a ligands specifically trigger completely unrelated endogenous coreceptors-lrp5/6 and ror1/2, respectively-through a common mechanism that involves their wnt-dependent coupling to the frizzled (fzd) coreceptor and recruitment of shared components, including dishevelled (dvl), axin, and glycogen synthase kinase 3 (gsk3). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | WNT Signaling, WNT Signaling and Myogenesis |
| + |
TNKS2 | down-regulates quantity by destabilization
|
GSK3B/Axin/APC |
0.452 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261248 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 19759537 |
Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT | down-regulates activity
phosphorylation
|
GSK3B/Axin/APC |
0.54 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227952 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16293724 |
We show that PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase Akt by free G protein betagamma subunits and the direct association of the G protein alphas subunit with the regulator of G protein signaling (RGS) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3beta from its complex with axin, thereby relieving the inhibitory phosphorylation of beta-catenin and activating its signaling pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
LRP6 | down-regulates activity
binding
|
GSK3B/Axin/APC |
0.737 |
| 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 |
| + |
AMER1 | up-regulates activity
relocalization
|
GSK3B/Axin/APC |
0.65 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227991 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21304492 |
Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CSNK1E | up-regulates
phosphorylation
|
GSK3B/Axin/APC |
0.641 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227976 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12000790 |
We conclude that a major role of axin in the wnt is to provide the kinase activity that initiates the betBeta-catenin phosphorylation cascade at s45. This process is mediated by cki, the alfa, delta, or ? Isoform, all detected in association with axin by lc/ms. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Gbeta | down-regulates activity
phosphorylation
|
GSK3B/Axin/APC |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270068 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 28646232 |
We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
GSK3B/Axin/APC | down-regulates
binding
|
CTNNB1 |
0.896 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227881 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22083140 |
The role of apc is less clear, but it clearly binds to both b-catenin and axin, and could shuttle b-catenin from the plasma membrane and nucleus to the cytoplasmic axin complex. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227862 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 9482734 |
Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Chlorocebus Aethiops |
| Pathways: | Colorectal Carcinoma, Hepatocellular Tumor, Wnt in cancer, WNT Signaling, WNT Signaling and Myogenesis |
| + |
IGF1 | down-regulates activity
binding
|
GSK3B/Axin/APC |
0.336 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227948 |
|
|
Homo sapiens |
Breast Cancer Cell, Kidney Cancer Cell |
| pmid |
sentence |
| 16039586 |
Erk, which is activated by hbx, associates with gsk-3beta through a docking motif ((291)fkfp) of gsk-3beta and phosphorylates gsk-3beta at the (43)thr residue, which primes gsk-3beta for its subsequent phosphorylation at ser9 by p90rsk, resulting in inactivation of gsk-3beta and upregulation of beta-catenin. This pathway is a general signal, as it was also observed in cell lines in which erk-primed inactivation of gsk-3beta was regulated by igf-1, tgf-beta, and receptor tyrosine kinase her2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AXIN2 | up-regulates activity
binding
|
GSK3B/Axin/APC |
0.742 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228003 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10911903 |
It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain, Kidney, Lung |
| + |
AXIN1 | form complex
binding
|
GSK3B/Axin/APC |
0.932 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227292 |
|
|
Homo sapiens |
Colonic Cancer Cell |
| pmid |
sentence |
| 9734785 |
Axin, an inhibitor of the wnt pathway, interacts with beta-catenin, gsk-3beta and apc and reduces the beta-catenin level. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GSK3B/Axin/APC | up-regulates
binding
|
CSNK1D |
0.542 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227908 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12000790 |
Complex of axin and casein kinase i (cki) induces beta-catenin phosphorylation at a single site: serine 45 (s45). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ERK1/2 | down-regulates activity
phosphorylation
|
GSK3B/Axin/APC |
0.35 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262519 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 28646232 |
We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Colorectal Carcinoma, Hepatocellular Tumor |
| + |
PPM1A | down-regulates
dephosphorylation
|
GSK3B/Axin/APC |
0.36 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227955 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10644691 |
Pp2c utilizes axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that pp2c is a positive regulator of wnt signal transduction and mediates its effects through the dephosphorylation of axin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MACF1 | down-regulates quantity by destabilization
|
GSK3B/Axin/APC |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227997 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 16815997 |
In the absence of wnt, macf1 associated with a complex that contained axin, betBeta-catenin, gsk3beta, and apc. Upon wnt stimulation, macf1 appeared to be involved in the translocation and subsequent binding of the axin complex to lrp6 at the cell membrane. Macf1 is involved in the translocation of the complex containing axin, Beta-catenin, and gsk3_ but not apc from the cytosol to the cell membrane, where axin and macf1 bind to lrp-5/6. Subsequently, gsk3_ is inactivated by phosphorylation, axin is degraded, and Beta-catenin is released and enters the nucleus, where it can activate the wnt-responsive genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LPR5/6 | down-regulates activity
binding
|
GSK3B/Axin/APC |
0.714 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256177 |
|
|
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. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Wnt in cancer |
| + |
APC2 | up-regulates
binding
|
GSK3B/Axin/APC |
0.592 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227945 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9601641 |
Human axin (haxin) binds directly to beta-catenin, gsk3 beta, and apc in vitro, and the endogenous proteins are found in a complex in cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LRP6 | down-regulates quantity by destabilization
relocalization
|
GSK3B/Axin/APC |
0.737 |
| 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 |
| + |
APC | form complex
binding
|
GSK3B/Axin/APC |
0.852 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227296 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9734785 |
Axin, an inhibitor of the wnt pathway, interacts with beta-catenin, gsk-3beta and apc and reduces the beta-catenin level. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GSK3B/Axin/APC | down-regulates quantity by destabilization
phosphorylation
|
SNAI2 |
0.341 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281174 |
|
|
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 22727060 |
In this study, we have demonstrated the inhibitory effects of Slug/Snail2 phosphorylation by GSK-3β on EMT. GSK-3β can regulate Snail1 function via phosphorylation at two consensus motifs: phosphorylation at the first motif regulates its ubiquitination by β-transducin repeat containing protein (β-TrCP), whereas phosphorylation at the second motif controls its subcellular localization [10]. A non-phosphorylated variant of Snail1 resides more stably in the nucleus to exclusively induce EMT [5]. GSK-3β can inhibit Snail1 expression via inhibiting its transcription [11], as well as by regulating Snail1 degradation and nuclear translocation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GSK3B/Axin/APC | down-regulates quantity by destabilization
phosphorylation
|
SNAI1 |
0.395 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281175 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17692821 |
Glycogen synthase kinase-3beta (GSK-3beta) regulates the Snail1 level by degrading Snail1 protein. Glycogen synthase kinase-3β (GSK-3β) has recently been demonstrated to regulate the Snail1 level by phosphorylation, β-TrCP-directed ubiquitination, and proteasomal degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RNF146 | down-regulates quantity
ubiquitination
|
GSK3B/Axin/APC |
0.52 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259998 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21799911 |
By RNAi screening, we identified the RNF146 RING-type ubiquitin E3 ligase as a positive regulator of Wnt signaling that operates with tankyrase to maintain low steady-state levels of Axin proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Wnt in cancer |
4.0
GSK3B/Axin/APC