| + |
AKT1 | down-regulates activity 
phosphorylation
|
TSC |
0.784 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235340 |
|
|
Mus musculus |
3T3-L1 Cell |
| pmid |
sentence |
| 19593385 |
In examining the requirements for different Akt-mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking all five previously identified Akt sites fully block insulin-stimulated mTORC1 signaling in reconstituted Tsc2 null cells, and this mutant also inhibits adipogenesis |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235628 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 12150915 |
We have shown thataktregulates the tsc1-tsc2 complex by directly phosphorylating tsc2. Tsc2 is inactivated by akt-dependent phosphorylation, which destabilizes tsc2 and disrupts its interaction with tsc1. Tsc2 is inactivated by akt-dependent phosphorylation, which destabilizes tsc2 and disrupts its interaction with tsc1akt has been shown to directly phosphorylate two sites on tsc2 (s939 and t1462 on the full-length human protein), which are conserved and phosphorylated in drosophila tsc2, and is likely to phosphorylate two or three additional sites (s981 and s1130/s1132). |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| + |
AKT | down-regulates activity
phosphorylation
|
TSC |
0.784 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251526 |
|
|
Mus musculus |
3T3-L1 Cell |
| pmid |
sentence |
| 19593385 |
In examining the requirements for different Akt-mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking all five previously identified Akt sites fully block insulin-stimulated mTORC1 signaling in reconstituted Tsc2 null cells, and this mutant also inhibits adipogenesis |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, mTOR in cancer, MTOR Signaling |
| + |
TSC2 | form complex 
binding
|
TSC |
0.934 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217913 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12172553 |
TSC1 and TSC2 proteins form a physical and functional complex in vivo. Here, we show that TSC1-TSC2 inhibits the p70 ribosomal protein S6 kinase 1 (an activator of translation) and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation). These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MYCBP2 | down-regulates
ubiquitination
|
TSC |
0.314 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261202 |
|
|
Rattus norvegicus |
PC-12 Cell |
| pmid |
sentence |
| 14559897 |
Pam Interacts with the Tuberin-Hamartin Complex—To examine the in vivo association of tuberin and Pam, we performed co-immunoprecipitation experiments in PC12 cells and rat embryonic brain. Immunoprecipitation of tuberin using an anti-tuberin antibody followed by immunoblot analysis showed that endogenous Pam co-immunoprecipitates with tuberin in PC12 cells and embryonic rat brain. Pam Homolog HIW Modulates Tsc1Tsc2 Activity in Drosophila. The enhancement of Tsc1Tsc2 phenotype by the removal of the hiw gene indicates that hiw negatively regulates Tsc1Tsc2 activity in Drosophila eye. Taken together, it is probable that Pam may function as an E3 ligase for tuberin and regulate the ubiquitination and proteasomal degradation of the tuberinhamartin complex particularly in the CNS |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
TSC | down-regulates activity 
|
MTOR |
0.776 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217907 |
|
|
Homo sapiens |
HEK-293 Cell, U2-OS Cell |
| pmid |
sentence |
| 12271141 |
These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mtor |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | MTOR Signaling |
| + |
TSC1 | form complex
binding
|
TSC |
0.934 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217910 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12172553 |
TSC1 and TSC2 proteins form a physical and functional complex in vivo. Here, we show that TSC1-TSC2 inhibits the p70 ribosomal protein S6 kinase 1 (an activator of translation) and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation). These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Insulin Signaling |
| + |
RPS6KA1 | down-regulates activity
phosphorylation
|
TSC |
0.722 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217900 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15342917 |
The mitogen-activated protein kinase (mapk)-activated kinase, p90 ribosomal s6 kinase (rsk) 1, was found to interact with and phosphorylate tuberin at a regulatory site, ser-1798, located at the evolutionarily conserved c terminus of tuberin. Rsk1 phosphorylation of ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mtor signaling to s6k1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling, MTOR Signaling |
| + |
AMPK | up-regulates activity 
phosphorylation
|
TSC |
0.484 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217749 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 16959574 |
GSK3 inhibits the mTOR pathway by phosphorylating TSC2 in a manner dependent on AMPK-priming phosphorylation |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | AMPK Signaling, MTOR Signaling |
| + |
WDR45B | up-regulates quantity
binding
|
TSC |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268479 |
|
|
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 28561066 |
WIPI3 associates with the TSC complex and FIP200. The specific interaction between WIPI3 and the TSC complex was demonstrated by immunopurification of both endogenous TSC1 and TSC2 with GFP-WIPI3 (Fig. 5a). These data suggest that WIPI3 functions in association with the TSC complex to regulate mTOR activity in the lysosomal compartment. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TSC | down-regulates activity
|
mTORC1 |
0.62 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251527 |
|
|
Homo sapiens |
HEK-293 Cell, U2-OS Cell |
| pmid |
sentence |
| 12271141 |
These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mtor |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, mTOR in cancer |
| + |
TSC | down-regulates activity
gtpase-activating protein
|
RHEB |
0.917 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235895 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15340059 |
Tsc2 functions as a gap to inhibit rheb activity. Tsc2 displays gap (gtpase-activating protein) activity specifically towards the small g protein rheb and inhibits its ability to stimulate the mtor signaling pathway. It has recently been shown that tsc2 has gtpase-activating protein (gap) activity towards the ras family small gtpase rheb (ras homolog enriched in brain), and tsc1/2 antagonizes the mtor signaling pathway via stimulation of gtp hydrolysis of rheb. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, mTOR in cancer, MTOR Signaling |
| + |
AKT2 | down-regulates activity
phosphorylation
|
TSC |
0.677 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235852 |
|
|
Mus musculus |
3T3-L1 Cell |
| pmid |
sentence |
| 19593385 |
In examining the requirements for different Akt-mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking all five previously identified Akt sites fully block insulin-stimulated mTORC1 signaling in reconstituted Tsc2 null cells, and this mutant also inhibits adipogenesis |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
RPS6K | down-regulates activity
phosphorylation
|
TSC |
0.723 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256311 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15342917 |
The mitogen-activated protein kinase (mapk)-activated kinase, p90 ribosomal s6 kinase (rsk) 1, was found to interact with and phosphorylate tuberin at a regulatory site, ser-1798, located at the evolutionarily conserved c terminus of tuberin. Rsk1 phosphorylation of ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mtor signaling to s6k1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
TSC
CPX-6142