| + |
mTORC1 | up-regulates activity 
phosphorylation
|
NRBF2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265876 |
Ser113 |
AEDAEGQsPLSQKYS |
Homo sapiens |
|
| pmid |
sentence |
| 28059666 |
Human NRBF2 is phosphorylated by MTORC1 at S113 and S120. Upon nutrient starvation or MTORC1 inhibition, NRBF2 phosphorylation is diminished. Phosphorylated NRBF2 preferentially interacts with PIK3C3/PIK3R4. Suppression of NRBF2 phosphorylation by MTORC1 inhibition alters its binding preference from PIK3C3/PIK3R4 to ATG14/BECN1, leading to increased autophagic PtdIns3K complex assembly, as well as enhancement of ULK1 protein complex association. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265877 |
Ser120 |
SPLSQKYsPSTEKCL |
Homo sapiens |
|
| pmid |
sentence |
| 28059666 |
Human NRBF2 is phosphorylated by MTORC1 at S113 and S120. Upon nutrient starvation or MTORC1 inhibition, NRBF2 phosphorylation is diminished. Phosphorylated NRBF2 preferentially interacts with PIK3C3/PIK3R4. Suppression of NRBF2 phosphorylation by MTORC1 inhibition alters its binding preference from PIK3C3/PIK3R4 to ATG14/BECN1, leading to increased autophagic PtdIns3K complex assembly, as well as enhancement of ULK1 protein complex association. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates
phosphorylation
|
ISCU |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217082 |
Ser14 |
FRLRRAAsALLLRSP |
Homo sapiens |
|
| pmid |
sentence |
| 23508953 |
Here, we demonstrate that mtorc1 associates with iscu and phosphorylates iscu at serine 14. This phosphorylation stabilized iscu protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | down-regulates activity 
phosphorylation
|
TFEB |
0.368 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255309 |
Ser142 |
AGNSAPNsPMAMLHI |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22343943 |
Here, we have used an mTORC1 in-vitro kinase assay and a phosphoantibody to demonstrate that serine S142, which we previously found to be phosphorylated by ERK2, is also phosphorylated by mTOR and that this phosphorylation has a crucial role in controlling TFEB subcellular localization and activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248274 |
Ser211 |
LVGVTSSsCPADLTQ |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22692423 |
Our data points to the lysosome as the site where mTORC1-dependent phosphorylation of TFEB occurs. [...]Our study has revealed a specific role for phosphorylation of TFEB S211 in the negative regulation of the nuclear abundance of TFEB. This occurs through the promotion of 14-3-3 binding and the masking of the nearby NLS on TFEB. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates quantity
phosphorylation
|
PIP4K2C |
0.286 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273680 |
Ser324 |
GPPALVGsYGTSPEG |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 25372051 |
PIP4kγ was phosphorylated by mTORC1 and associated with the complex. Phosphorylated PIP4kγ was enriched in light microsomal vesicles, whereas the unphosphorylated form was enriched in heavy microsomal vesicles associated with the Golgi. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273681 |
Ser328 |
LVGSYGTsPEGIGGY |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 25372051 |
PIP4kγ was phosphorylated by mTORC1 and associated with the complex. Phosphorylated PIP4kγ was enriched in light microsomal vesicles, whereas the unphosphorylated form was enriched in heavy microsomal vesicles associated with the Golgi. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates activity
phosphorylation
|
SGK1 |
0.606 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217078 |
Ser422 |
AEAFLGFsYAPPTDS |
in vitro |
|
| pmid |
sentence |
| 18570873 |
Mtor phosphorylated sgk1, but not sgk1-s422a, in vitro. Sgk1 phosphorylated p27 in vitro. These data implicate sgk1 as an mtorc1 (mtor-raptor) substrate. mtor may promote g1 progression in part through sgk1 activation |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Insulin Signaling |
| + |
mTORC1 | down-regulates
phosphorylation
|
MAF1 |
0.472 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217149 |
Ser60 |
PHVLEALsPPQTSGL |
Homo sapiens |
|
| pmid |
sentence |
| 20516213 |
The protein is phosphorylated mainly on residues s60, s68, and s75, and this inhibits its pol iii repression function. The responsible kinase is mtorc1, which phosphorylates maf1 directly. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217145 |
Ser68 |
PPQTSGLsPSRLSKS |
Homo sapiens |
|
| pmid |
sentence |
| 20516213 |
The protein is phosphorylated mainly on residues s60, s68, and s75, and this inhibits its pol iii repression function. The responsible kinase is mtorc1, which phosphorylates maf1 directly. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217153 |
Ser75 |
SPSRLSKsQGGEEEG |
Homo sapiens |
|
| pmid |
sentence |
| 20516213 |
The protein is phosphorylated mainly on residues s60, s68, and s75, and this inhibits its pol iii repression function. The responsible kinase is mtorc1, which phosphorylates maf1 directly. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | down-regulates activity
phosphorylation
|
EIF4EBP1 |
0.754 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236690 |
Ser65 |
FLMECRNsPVTKTPP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12747827 |
Phosphorylated on serine and threonine residues in response to insulin, egf and pdgf. Phosphorylation at thr-37, thr-46, ser-65 and thr-70, corresponding to the hyperphosphorylated form, is regulated by mtorc1 and abolishes binding to eif4e. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217137 |
Ser65 |
FLMECRNsPVTKTPP |
Homo sapiens |
|
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217086 |
Thr36 |
LPPGDYStTPGGTLF |
Homo sapiens |
|
| pmid |
sentence |
| 9465032 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). Raft1 phosphorylation of 4e-bp1 on thr-36 and thr-45 blocks its association with the cap-binding protein, eif-4e,in vitro. in response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236694 |
Thr37 |
PPGDYSTtPGGTLFS |
Homo sapiens |
|
| pmid |
sentence |
| 12747827 |
Phosphorylated on serine and threonine residues in response to insulin, egf and pdgf. Phosphorylation at thr-37, thr-46, ser-65 and thr-70, corresponding to the hyperphosphorylated form, is regulated by mtorc1 and abolishes binding to eif4e. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217110 |
Thr37 |
PPGDYSTtPGGTLFS |
Homo sapiens |
|
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217090 |
Thr45 |
PGGTLFStTPGGTRI |
Homo sapiens |
|
| pmid |
sentence |
| 9465032 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). Raft1 phosphorylation of 4e-bp1 on thr-36 and thr-45 blocks its association with the cap-binding protein, eif-4e,in vitro. in response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236698 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
|
| pmid |
sentence |
| 12747827 |
Phosphorylated on serine and threonine residues in response to insulin, egf and pdgf. Phosphorylation at thr-37, thr-46, ser-65 and thr-70, corresponding to the hyperphosphorylated form, is regulated by mtorc1 and abolishes binding to eif4e. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217114 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
|
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235964 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
|
| pmid |
sentence |
| 12747827 |
Phosphorylated on serine and threonine residues in response to insulin, egf and pdgf. Phosphorylation at thr-37, thr-46, ser-65 and thr-70, corresponding to the hyperphosphorylated form, is regulated by mtorc1 and abolishes binding to eif4e. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217141 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
|
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236702 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 10942774 |
Mammalian target of rapamycin-dependent phosphorylation of phas-i in four (s/t)p sites detected by phospho-specific antibodies. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235745 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 20670887 |
Specifically as part of mTORC1, mTOR directly phosphorylates the ribosomal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2)phosphorylation of the 4E-BPs leads to their inhibition and release from eIF4E at the 5_ cap of mRNAs |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235748 |
|
|
Cricetulus griseus |
|
| pmid |
sentence |
| 17510057 |
In response to insulin and nutrients, mTORC1, consisting of mTOR, raptor (regulatory-associated protein of mTOR), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein (4EBP) and p70 S6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236678 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12747827 |
Our data demonstrate that the TOS motif functions as a docking site for the mTOR/raptor complex, which is required for multisite phosphorylation of 4E-BP1, eIF4E release from 4E-BP1, and cell growth. |
|
| Publications: |
14 |
Organism: |
Homo Sapiens, Mus Musculus, Cricetulus Griseus |
| Pathways: | AMPK Signaling, Insulin Signaling, PI3K/AKT Signaling |
| + |
mTORC1 | down-regulates activity
phosphorylation
|
EEF2K |
0.347 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277908 |
Ser70 |
LTKSERYsSSGSPAN |
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 35513296 |
Our phosphoproteomics analysis add to this body of knowledge as it indicates that mTORC1 modulates additional phosphorylation sites in eEF2K, such as Y69, S70, S72, and S74, which is consistent with our previous findings |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277906 |
Ser72 |
KSERYSSsGSPANSF |
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 35513296 |
Our phosphoproteomics analysis add to this body of knowledge as it indicates that mTORC1 modulates additional phosphorylation sites in eEF2K, such as Y69, S70, S72, and S74, which is consistent with our previous findings |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277907 |
Ser74 |
ERYSSSGsPANSFHF |
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 35513296 |
Our phosphoproteomics analysis add to this body of knowledge as it indicates that mTORC1 modulates additional phosphorylation sites in eEF2K, such as Y69, S70, S72, and S74, which is consistent with our previous findings |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277909 |
Tyr69 |
NLTKSERySSSGSPA |
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 35513296 |
Our phosphoproteomics analysis add to this body of knowledge as it indicates that mTORC1 modulates additional phosphorylation sites in eEF2K, such as Y69, S70, S72, and S74, which is consistent with our previous findings |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates activity
phosphorylation
|
RPS6KB1 |
0.752 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255840 |
Thr390 |
DSKFTRQtPVDSPDD |
Homo sapiens |
|
| pmid |
sentence |
| 11914378 |
Thr229 phosphorylation requires prior phosphorylation of the Ser/Thr-Pro sites in the autoinhibitory domain and Thr389 in the linker domain,[…] Moreover, in vitro mTOR directly phosphorylates Ser371, and this event modulates Thr389phosphorylation by mTOR, compatible with earlier in vivo findings. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273843 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 35318320 |
Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Insulin Signaling |
| + |
mTORC1 | up-regulates activity
phosphorylation
|
RPS6K |
0.473 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255842 |
Thr390 |
DSKFTRQtPVDSPDD |
Homo sapiens |
|
| pmid |
sentence |
| 11914378 |
Thr229 phosphorylation requires prior phosphorylation of the Ser/Thr-Pro sites in the autoinhibitory domain and Thr389 in the linker domain [..]. Moreover, in vitro mTOR directly phosphorylates Ser371, and this event modulates Thr389phosphorylation by mTOR, compatible with earlier in vivo findings. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | PI3K/AKT Signaling |
| + |
mTORC1 | up-regulates
phosphorylation
|
RPS6KB1 |
0.752 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217060 |
Thr412 |
NQVFLGFtYVAPSVL |
Homo sapiens |
|
| pmid |
sentence |
| 10579915 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). In vitro activation of p70alfa by mtor-catalyzed phosphorylation involving p70alfa thr-412. Mtor-catalyzed p70alfa phosphorylation in vitro is accompanied by a substantial restoration in p70alfa kinase activity toward its physiologic substrate, the 40 s ribosomal protein s6. In response toinsulinand nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217056 |
Thr412 |
NQVFLGFtYVAPSVL |
Homo sapiens |
|
| pmid |
sentence |
| 10567431 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). In vitro activation of p70alfa by mtor-catalyzed phosphorylation involving p70alfa thr-412. Mtor-catalyzed p70alfa phosphorylation in vitro is accompanied by a substantial restoration in p70alfa kinase activity toward its physiologic substrate, the 40 s ribosomal protein s6. In response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217067 |
Thr412 |
NQVFLGFtYVAPSVL |
Homo sapiens |
|
| pmid |
sentence |
| 15809305 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). In vitro activation of p70alfa by mtor-catalyzed phosphorylation involving p70alfa thr-412. Mtor-catalyzed p70alfa phosphorylation in vitro is accompanied by a substantial restoration in p70alfa kinase activity toward its physiologic substrate, the 40 s ribosomal protein s6. In response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217071 |
Thr412 |
NQVFLGFtYVAPSVL |
Homo sapiens |
|
| pmid |
sentence |
| 17510057 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). In vitro activation of p70alfa by mtor-catalyzed phosphorylation involving p70alfa thr-412. Mtor-catalyzed p70alfa phosphorylation in vitro is accompanied by a substantial restoration in p70alfa kinase activity toward its physiologic substrate, the 40 s ribosomal protein s6. in response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Pathways: | Insulin Signaling |
| + |
mTORC1 | up-regulates activity
phosphorylation
|
JMJD1C |
0.243 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265168 |
Thr505 |
KFVSRPPtPKCVIDI |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 32034158 |
We show that, by direct interaction with USF-1, JMJD1C is recruited to lipogenic promoters. We also show that JMJD1C is phosphorylated at T505 by mammalian target of rapamyci (mTOR) to be recruited to lipogenic genes in response to insulin/feeding. we detected phosphorylation of WT JMJD1C but not T505A mutant when we co-transfected JMJD1C constructs along with the mTORC1 in 293FT cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT | up-regulates activity
phosphorylation
|
mTORC1 |
0.724 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217586 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20138985 |
Pras40 is an insulin-regulated inhibitor of the mtorc1 protein kinase. Insulin stimulates akt/pkb-mediated phosphorylation of pras40, which prevents its inhibition of mtorc1 in cells and in vitro. Phosphorylation of pras40 on thr246 by pkb/akt facilitates efficient phosphorylation of ser183 by mtorc1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252817 |
|
|
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: |
2 |
Organism: |
Homo Sapiens, Mus Musculus |
| Tissue: |
Muscle, Skeletal Muscle, Myotube |
| Pathways: | AMPK Signaling, EGFR Signaling, Glioblastoma Multiforme, Insulin Signaling, Luminal Breast Cancer, mTOR in cancer, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Thyroid Hormone Metabolism, WNT/FLT3 |
| + |
RPS6K | up-regulates
phosphorylation
|
mTORC1 |
0.469 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252794 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18722121 |
Ser719, ser721, and ser722 are the predominant rsk-dependent phosphorylation sites in raptor raptor phosphorylation regulates mtorc1 activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | PI3K/AKT Signaling |
| + |
TELO2 | up-regulates quantity by stabilization
binding
|
mTORC1 |
0.534 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272001 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20427287 |
MTOR exists in two distinct complexes, mTORC1 and mTORC2, that differ in their subunit composition. In this study, we identified KIAA0406 as a novel mTOR-interacting protein. Because it has sequence homology with Schizosaccharomyces pombe Tti1, we named it mammalian Tti1. Tti1 constitutively interacts with mTOR in both mTORC1 and mTORC2. Knockdown of Tti1 suppresses phosphorylation of both mTORC1 substrates (S6K1 and 4E-BP1) and an mTORC2 substrate (Akt) and also induces autophagy. Furthermore, using immunoprecipitation and size-exclusion chromatography analyses, we found that knockdown of either Tti1 or Tel2 causes disassembly of mTORC1 and mTORC2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates activity
phosphorylation
|
BTRC |
0.289 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267829 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 33861966 |
mTORC1 regulates the stability of CREB2. Our data suggest that mTORC1 promotes the binding of the E3 ligase, βTrCP, to CREB2 (Figure 4D), promoting CREB2 degradation by the proteasome (Figure 4E). Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
RHEB | up-regulates activity
|
mTORC1 |
0.794 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235355 |
|
|
Mus musculus |
3T3-L1 Cell |
| pmid |
sentence |
| 19299511 |
These results suggest that Rheb induces alteration in the binding of 4E-BP1 with mTORC1 to regulate mTORC1 activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232208 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19222999 |
Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1. |
|
| Publications: |
2 |
Organism: |
Mus Musculus, Homo Sapiens |
| Pathways: | AMPK Signaling, Insulin Signaling, Luminal Breast Cancer, mTOR in cancer |
| + |
MAPK11 |
phosphorylation
|
mTORC1 |
0.334 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217580 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21757713 |
Arsenite treatment of cells activates p38_ and induces interaction between p38_ and raptor, a regulatory component of mtorc1, resulting in phosphorylation of raptor on ser(863) and ser(771). The phosphorylation of raptor on these sites enhances mtorc1 activity, and contributes largely to arsenite-induced mtorc1 activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SLC38A9 | up-regulates activity 
|
mTORC1 |
0.475 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268014 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25567906 |
SLC38A9 is a Lysosomal Membrane Protein Required for mTORC1 Activation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255311 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 29053970 |
Activation of mTORC1 by arginine requires SLC38A9, a poorly understood lysosomal membrane protein with homology to amino acid transporters. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GFs | up-regulates
|
mTORC1 |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-219382 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23863153 |
Growth factors and nutrients regulate the mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] by different mechanisms. The players that link growth factors and mTORC1 activation have been known for several years and mouse models have validated its relevance for human physiology and disease. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Autophagy |
| + |
TSC | down-regulates activity 
|
mTORC1 |
0.617 |
| 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 |
| + |
GABARAP | up-regulates activity
binding
|
mTORC1 |
0.333 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-219391 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11146101 |
N-terminal proline/serine rich (ps) domain of ulk1 (amino acid 287-416) is required for ulk1-gate-16 and ulk1-gabarap protein interactions |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Autophagy |
| + |
L-arginine | up-regulates activity
|
mTORC1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268018 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 27126896 |
Importantly, asparagine/glutamine pre-load only results in mTOR activation following amino acid stimulation (Fig. 5a), indicating that it is their exchange factor roles that elicit mTORC1 activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
glutamine | up-regulates activity
|
mTORC1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268012 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 27126896 |
Importantly, asparagine/glutamine pre-load only results in mTOR activation following amino acid stimulation (Fig. 5a), indicating that it is their exchange factor roles that elicit mTORC1 activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268008 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22749528 |
Leucine and Glutamine Activate Glutaminolysis and mTORC1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AKT1S1 | form complex 
binding
|
mTORC1 |
0.798 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205597 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25628925 |
Depending on their binding partners and sensitivities to rapamycin, mtor resides in at least two distinct complexes, termed mtor complex 1 (mtorc1, containing raptor, fkbp12, pras40 and mlst8) and mtor complex 2 (mtorc2, containing rictor, sin1, protor and mlst8) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | down-regulates activity
phosphorylation
|
ULK1/Atg13/Fip200 |
0.566 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-209904 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23863160 |
Several studies published simultaneously illustrated that the equivalent mammalian ULK1Atg13FIP200 complex was also negatively regulated by mTORC1 in an analogous manner [17,18,24]. In mammalian cells, amino acid starvation or rapamycin treatment causes dephosphorylation of both Atg13 and ULK1, indicating that an mTORC1 input regulates the ULK1Atg13FIP200 complex mTORC1 modulates the kinase activity of ULK1 directly, with rapamycin treatment of cells leading to enhanced ULK1 kinase activity, whereas Rheb overexpression causes a decrease in ULK1 kinase activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling, Autophagy |
| + |
mTORC1 | up-regulates quantity by expression
|
PPARG |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235343 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 19593385 |
Activation of mTORC1 causes a robust increase in the mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master transcriptional regulator of adipocyte differentiation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
14-3-3 | down-regulates
binding
|
mTORC1 |
0.518 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217565 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20006481 |
Akt can phosphorylate pras40, a raptor binding protein that also acts as an inhibitor of torc1. Akt-mediated phosphorylation of pras40 again promotes 14-3-3 binding, in this case leading to relief from pras40-mediated inhibition. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AMPK | down-regulates activity
phosphorylation
|
mTORC1 |
0.456 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216422 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20083114 |
A recent study revealed that ampk can inhibit mtorc1 independently of tsc2 by phosphorylating raptor at ser863. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216430 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18439900 |
The phosphorylation of raptor by ampk is required for the inhibition of mtorc1 and cell-cycle arrest induced by energy stress. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-209862 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23863160 |
AMPK inhibits mTORC1 through two means: first, through phosphorylation of TSC2 to activate its GAP (GTPase-activating protein) activity that converts Rheb into an inactive GDP-bound state, thus switching off mitogenic stimulation of mTORC1 [31], and, secondly, through phosphorylation of raptor at Ser722 and Ser792, which leads to 14-3-3 protein binding and mTORC1 inhibition |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216418 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 21460634 |
AMP-activated protein kinase (AMPK), which is activated by LKB1/Strad/Mo25 upon high AMP levels, stimulates autophagy by inhibiting mTORC1. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens, Mus Musculus |
| Pathways: | AMPK Signaling, Autophagy |
| + |
leucine | up-regulates activity
|
mTORC1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268010 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22749528 |
Leucine and Glutamine Activate Glutaminolysis and mTORC1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DYRK3 | down-regulates
phosphorylation
|
mTORC1 |
0.291 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217571 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23415227 |
When dyrk3 is active, it allows stress granule dissolution, releasing mtorc1 for signaling and promoting its activity by directly phosphorylating the mtorc1 inhibitor pras40 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates
phosphorylation
|
RPS6KB2 |
0.59 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217074 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17510057 |
In response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates
|
Adipogenesis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235349 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 19593385 |
Activation of mTORC1 causes a robust increase in the mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master transcriptional regulator of adipocyte differentiation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Thyroid Hormone Metabolism |
| + |
AKT2 | up-regulates activity
phosphorylation
|
mTORC1 |
0.575 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235967 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17277771 |
Furthermore, pras40 phosphorylation by akt and association with 14-3-3, a cytosolic anchor protein, are crucial for insulin to stimulate mtor. These findings identify pras40 as an important regulator of insulin sensitivity of the akt-mtor pathway and a potential target for the treatment of cancers, insulin resistance and hamartoma syndromes. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236705 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17386266 |
Insulin-stimulated phosphorylation of pras40 by akt/pkb suppresses its mtorc1 inhibitory activity. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
LNPK | up-regulates activity
binding
|
mTORC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272200 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 32433973 |
We demonstrate that Lunapark interacts with mechanistic target of rapamycin complex-1 (mTORC1), a central cellular regulator that coordinates growth and metabolism with environmental conditions. We show that mTORC1 binds Lunapark specifically at three-way junctions, and lysosomes, where mTORC1 is activated, make contact with three-way junctions where Lunapark resides. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
L-glutamine zwitterion | up-regulates activity
|
mTORC1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268017 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 27126896 |
Importantly, asparagine/glutamine pre-load only results in mTOR activation following amino acid stimulation (Fig. 5a), indicating that it is their exchange factor roles that elicit mTORC1 activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268015 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22749528 |
Leucine and Glutamine Activate Glutaminolysis and mTORC1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GOLPH3 | up-regulates activity
|
mTORC1 |
0.299 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253555 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19553991 |
Mechanistically, GOLPH3 regulates cell size, enhances growth factor-induced mTOR signaling in human cancer cells and alters response to mTOR inhibitor in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | down-regulates
phosphorylation
|
ULK1 |
0.628 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217133 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19690328 |
The complementary inhibitory mechanism in which mtorc1 phosphorylates the autophagy regulatory complex containing unc-51-like kinase 1 (ulk1), the mammalian atg13 protein, and focal adhesion kinase interacting protein of 200 kd (fip200) has also been elucidated. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RPS6K | up-regulates activity
phosphorylation
|
mTORC1 |
0.469 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252796 |
|
|
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: | PI3K/AKT Signaling |
| + |
mTORC1 | up-regulates activity
|
Skeletal_muscle_differentiation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256273 |
|
|
Mus musculus |
Satellite Cell |
| pmid |
sentence |
| 25047835 |
Knockdown (KD) of either mTORC or its subunit Raptor delayed SC activation without influencing the differentiation program. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Thyroid Hormone Metabolism |
| + |
PIH1D1 | up-regulates quantity by stabilization
binding
|
mTORC1 |
0.342 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265897 |
|
|
Homo sapiens |
MCF-7 Cell |
| pmid |
sentence |
| 24036451 |
PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription.PIH1D1 is important for mTORC1 assembly |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK3 | up-regulates
phosphorylation
|
mTORC1 |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217559 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19864431 |
Here we focus primarily although not exclusively on raptor Ser(863) phosphorylation. We report that insulin promotes mTORC1-associated phosphorylation of raptor Ser(863) via the canonical PI3K/TSC/Rheb pathway in a rapamycin-sensitive manner. mTORC1 activation by other stimuli (e.g. amino acids, epidermal growth factor/MAPK signaling, and cellular energy) also promote raptor Ser(863) phosphorylation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217556 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19346248 |
The phosphorylation of raptor is stimulated by insulin and inhibited by rapamycin. Importantly, the site-directed mutation of raptor at one phosphorylation site, Ser(863), reduced mTORC1 activity both in vitro and in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217544 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21757713 |
The phosphorylation of Raptor on these sites enhances mTORC1 activity, and contributes largely to arsenite-induced mTORC1 activation. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates
phosphorylation
|
GRB10 |
0.363 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217063 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21659604 |
The adaptor protein grb10 was identified as an mtorc1 substrate that mediates the phosphoinositide 3-kinase. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DEPTOR | down-regulates activity
binding
|
mTORC1 |
0.722 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251658 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 19446321 |
DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MTOR | form complex
binding
|
mTORC1 |
0.898 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205615 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25628925 |
Depending on their binding partners and sensitivities to rapamycin, mtor resides in at least two distinct complexes, termed mtor complex 1 (mtorc1, containing raptor, fkbp12, pras40 and mlst8) and mtor complex 2 (mtorc2, containing rictor, sin1, protor and mlst8) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glioblastoma Multiforme, Pancreatic ductal adenocarcinoma (PDA) |
| + |
TTI1 | up-regulates quantity by stabilization
binding
|
mTORC1 |
0.604 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272002 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20427287 |
MTOR exists in two distinct complexes, mTORC1 and mTORC2, that differ in their subunit composition. In this study, we identified KIAA0406 as a novel mTOR-interacting protein. Because it has sequence homology with Schizosaccharomyces pombe Tti1, we named it mammalian Tti1. Tti1 constitutively interacts with mTOR in both mTORC1 and mTORC2. Knockdown of Tti1 suppresses phosphorylation of both mTORC1 substrates (S6K1 and 4E-BP1) and an mTORC2 substrate (Akt) and also induces autophagy. Furthermore, using immunoprecipitation and size-exclusion chromatography analyses, we found that knockdown of either Tti1 or Tel2 causes disassembly of mTORC1 and mTORC2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
arginine | up-regulates activity
|
mTORC1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268013 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 27126896 |
Importantly, asparagine/glutamine pre-load only results in mTOR activation following amino acid stimulation (Fig. 5a), indicating that it is their exchange factor roles that elicit mTORC1 activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates quantity by expression
|
ATP6V1A |
0.261 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260636 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 21804531 |
These data suggested that V-ATPase mRNA levels were upregulated by mTORC1 through a transcriptional mechanism. Tfeb is required for mTORC1-induced V-ATPase expression. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
MTMR3 | down-regulates activity
|
mTORC1 |
0.311 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245108 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 26787466 |
The PtdIns3-phosphatase MTMR3 interacts with mTORC1 and suppresses its activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Autophagy |
| + |
mTORC1 | up-regulates
|
MYC |
0.347 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256172 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24856037 |
MTORC1 and mTORC2 converge on c-Myc to control metabolic reprogramming in cancer. mTORC1 and mTORC2 conspire to link growth factor receptor–PI3K signaling with c-Myc-dependent metabolic reprogramming by controlling both c-Myc levels and activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EGFR Signaling, mTOR in cancer, WNT/FLT3 |
| + |
CIB2 | down-regulates activity
binding
|
mTORC1 |
0.265 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269663 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 34162842 |
Mechanistically, CIB2 negatively regulates mTORC1 by preferentially binding to 'nucleotide empty' or inactive GDP-loaded Rheb. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
Glutaminolysis | up-regulates activity
|
mTORC1 |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268007 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22749528 |
Glutaminolysis Is Required for the Activation of mTORC1 by Leucine and Glutamine |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAB1A | up-regulates activity
binding
|
mTORC1 |
0.319 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261286 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 27479033 |
Hemagglutinin (HA)-Rab1A is associated with mTOR and Raptor, not Rictor (Figure S2A), and is bound more with Myc-Raptor than Myc-mTOR (Figures S2B and S2C).|Rab1A Is an mTORC1 Activator and a Colorectal Oncogene |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | down-regulates activity
|
Lysosome fusion |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277786 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 39000072 |
The fusion of matured macropinosomes with lysosomes is promoted by TRPML1, and degradation of macropinosomes is inhibited by mTORC1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RRAGD | up-regulates
binding
|
mTORC1 |
0.641 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217550 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20006481 |
Active rag and gtr heterodimers are able to bind and activate torc1, through direct interactions with raptor |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates
|
HIF1A |
0.366 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167187 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20670887 |
Hif1alfa is the transcription factor downstream of mtorc1 in the control of glycolytic genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates
|
Cell_growth |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-209919 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23863160 |
Cellular energy and nutrient status will dictate whether mTORC1 takes over and drives cell growth or conversely whether AMPK becomes active once again to drive consecutive waves of autophagy thorough ULK1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling, EGFR Signaling, Glioblastoma Multiforme, Insulin Signaling, Luminal Breast Cancer |
| + |
CILK1 | up-regulates
phosphorylation
|
mTORC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217562 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22356909 |
Our findings demonstrate an important role for ick in modulating the activity of mtorc1 through phosphorylation of raptor thr-908 and thus implicate a potential signaling mechanism by which ick regulates cell proliferation and division. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT1 | up-regulates activity
phosphorylation
|
mTORC1 |
0.724 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252539 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20138985 |
Pras40 is an insulin-regulated inhibitor of the mtorc1 protein kinase. Insulin stimulates akt/pkb-mediated phosphorylation of pras40, which prevents its inhibition of mtorc1 in cells and in vitro. Phosphorylation of pras40 on thr246 by pkb/akt facilitates efficient phosphorylation of ser183 by mtorc1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252540 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17130464 |
Phosphorylation of pras40-thr246 by pkb/akt, and pras40-ser183 and pras40-ser221 by mtorc1 results in dissociation from mtorc1, and its binding to 14-3-3 proteins. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Glioblastoma Multiforme |
| + |
SMAD1/5/8/SMAD4 | up-regulates activity
|
mTORC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256487 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 24145169 |
The BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Tissue: |
Muscle |
| + |
mTORC1 | down-regulates quantity by repression
translation regulation
|
APOB |
0.273 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252117 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23721961 |
Activation of mTORC1 also has dual effects on ApoB synthesis: it inhibits ApoB secretion by decreasing ApoB translation, but promotes ApoB secretion by inhibiting sortilin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RPS6KA1 | up-regulates
phosphorylation
|
mTORC1 |
0.467 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217553 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18722121 |
Ser719, ser721, and ser722 are the predominant rsk-dependent phosphorylation sites in raptor raptor phosphorylation regulates mtorc1 activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling |
| + |
TBCK | up-regulates activity
|
mTORC1 |
0.253 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266699 |
|
|
Homo sapiens |
Brain |
| pmid |
sentence |
| 33240423 |
TBCK included two types of alternatively spliced isoforms (long TBCK and short TBCK). Although there is a long way to go to fully understand the function of TBCK, recent research indicates that TBCK plays an important role in brain development. BCK deficiency would disturb activation of the mTOR complex 1 (mTORC1), thus, affecting the autophagy process and further leading to autophagosomal-lysosomal dysfunction |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Gbeta |
phosphorylation
|
mTORC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270027 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21071439 |
We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK3 |
phosphorylation
|
mTORC1 |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217577 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21071439 |
We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ERK1/2 |
phosphorylation
|
mTORC1 |
0.397 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270150 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21071439 |
We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling, EGFR Signaling, Glioblastoma Multiforme, Insulin Signaling, Luminal Breast Cancer, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, WNT/FLT3 |
| + |
LARP1 | up-regulates activity
binding
|
mTORC1 |
0.305 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260993 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 28650797 |
LARP1-mTORC1 interaction occurs through direct protein-protein contacts. phosphorylated LARP1 facilitates mTORC1-dependent phosphorylation of S6K1 and 4EBP1 on the LARP1-containing mRNPs by scaffolding mTORC1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
sirolimus | down-regulates
chemical inhibition
|
mTORC1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-219385 |
|
|
in vitro |
|
| pmid |
sentence |
| 17350953 |
Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its mislocalization. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
mTORC1 | up-regulates
|
Proliferation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256064 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15829723 |
Phosphorylation of mTOR by Akt leads to mTOR activation (40, 52) and the subsequent activation of p70S6K (47). This latter event has great potential importance for the promotion of muscle growth by the IGF-I/Akt/mTOR pathway, because p70S6k is a potent stimulator of protein synthesis that can be activated by increases in muscle contraction |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256063 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20508131 |
The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogen and nutrient signals to control cell proliferation and cell size. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Skeletal Muscle, HEK-293 Cell |
| Pathways: | AMPK Signaling, EGFR Signaling, Glioblastoma Multiforme, Insulin Signaling, Luminal Breast Cancer, mTOR in cancer, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, WNT/FLT3 |
| + |
RAGAC | up-regulates activity
relocalization
|
mTORC1 |
0.682 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228158 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20381137 |
The Rag GTPases interact with mTORC1 and are proposed to activate it in response to amino acids by promoting mTORC1 translocation to a membrane-bound compartment that contains the mTORC1 activator, Rheb |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | mTOR in cancer |
| + |
MAPK1 |
phosphorylation
|
mTORC1 |
0.384 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217574 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21071439 |
We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mTORC1 | up-regulates activity
phosphorylation
|
mTORC1 |
0.832 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235518 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 18372248 |
We propose that after mtorc1 kinase activation by upstream regulators, pras40 is phosphorylated directly by mtor, thus contributing to the relief of pras40-mediated substrate competition. We also find that mutation of ser-221 to ala increases the inhibitory activity of pras40 toward mtorc1. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | AMPK Signaling, Autophagy, EGFR Signaling, Glioblastoma Multiforme, Insulin Signaling, Luminal Breast Cancer, mTOR in cancer, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Thyroid Hormone Metabolism, WNT/FLT3 |
| + |
DEPTOR | form complex
binding
|
mTORC1 |
0.722 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205600 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25628925 |
Depending on their binding partners and sensitivities to rapamycin, mtor resides in at least two distinct complexes, termed mtor complex 1 (mtorc1, containing raptor, fkbp12, pras40 and mlst8) and mtor complex 2 (mtorc2, containing rictor, sin1, protor and mlst8) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RPTOR | form complex
binding
|
mTORC1 |
0.86 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205627 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25628925 |
Depending on their binding partners and sensitivities to rapamycin, mtor resides in at least two distinct complexes, termed mtor complex 1 (mtorc1, containing raptor, fkbp12, pras40 and mlst8) and mtor complex 2 (mtorc2, containing rictor, sin1, protor and mlst8) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MLST8 | form complex
binding
|
mTORC1 |
0.884 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205609 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25628925 |
Depending on their binding partners and sensitivities to rapamycin, mtor resides in at least two distinct complexes, termed mtor complex 1 (mtorc1, containing raptor, fkbp12, pras40 and mlst8) and mtor complex 2 (mtorc2, containing rictor, sin1, protor and mlst8) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ULK1/Atg13/Fip200 | down-regulates activity
phosphorylation
|
mTORC1 |
0.566 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-209910 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23863160 |
Raptor phosphorylation by ULK1 was sufficient to completely block Rheb-induced mTORC1 activity in cells as well as mTORC1 kinase activity invitro |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling, Autophagy |
| + |
mTORC1 | down-regulates
|
Autophagy |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-209922 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23863160 |
Historically, it was known that autophagy was switched off when mTORC1 was active and that inhibition of mTORC1 was a potent autophagy inducer. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | AMPK Signaling, Autophagy |
| + |
RRAGC | up-regulates
binding
|
mTORC1 |
0.692 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217547 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20006481 |
Active rag and gtr heterodimers are able to bind and activate torc1, through direct interactions with raptor. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK3 | up-regulates activity
phosphorylation
|
mTORC1 |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-209859 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19143636 |
Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT1 | up-regulates
phosphorylation
|
mTORC1 |
0.724 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255844 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15829723 |
Once phosphorylated, Akt can act on a broad spectrum of substrates that can influence cell survival and proliferation and protein synthesis (65). Phosphorylation of mTOR by Akt leads to mTOR activation (40, 52) and the subsequent activation of p70S6K |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skeletal Muscle |
| Pathways: | Glioblastoma Multiforme |
3.0
mTORC1