+ |
MTOR | down-regulates activity
phosphorylation
|
AKT1S1 |
0.904 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-154956 |
Ser183 |
PTQQYAKsLPVSVPV |
Homo sapiens |
HEK-293 Cell |
pmid |
sentence |
17517883 |
The proline-rich Akt substrate of 40 kilodaltons (PRAS40) was identified as a raptor-binding protein that is phosphorylated directly by mammalian target of rapamycin (mTOR) complex 1 (mTORC1) but not mTORC2 in vitro, predominantly at PRAS40 (Ser(183)).PRAS40 binding to raptor was also abolished by mutation of the major mTORC1 phosphorylation site, Ser(183), to Asp. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-178120 |
Ser183 |
PTQQYAKsLPVSVPV |
in vitro |
|
pmid |
sentence |
18372248 |
Pras40 functions as a negative regulator when bound to mtorc1, and it dissociates from mtorc1 in response to insulin. Pras40 has been demonstrated to be a substrate of mtorc1, and one phosphorylation site, ser-183, has been identified. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-178124 |
Ser212 |
EENGPPSsPDLDRIA |
in vitro |
|
pmid |
sentence |
18372248 |
In this study, we used two-dimensional phosphopeptide mapping in conjunction with mutational analysis to show that in addition to ser-183, mtorc1 also phosphorylates ser-212 and ser-221 in pras40 when assayed in vitro. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-178128 |
Ser221 |
DLDRIAAsMRALVLR |
in vitro |
|
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 competitionwe also find that mutation of ser-221 to ala increases the inhibitory activity of pras40 toward mtorc1. |
|
Publications: |
4 |
Organism: |
Homo Sapiens, In Vitro |
Pathways: | MTOR Signaling |
+ |
DYRK3 | down-regulates activity
phosphorylation
|
AKT1S1 |
0.339 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-279167 |
Thr246 |
LPRPRLNtSDFQKLK |
Homo sapiens |
|
pmid |
sentence |
23415227 |
Thus, DYRK3 directly phosphorylates PRAS40 at Thr246, a phosphorylation site responsible for regulation of PRAS40, resulting in decreased binding of PRAS40 to mTORC1, allowing activation of mTORC1 signaling in unstressed cells and reactivation of mTORC1 during stress recovery.Finally, we studied the dynamics of how DYRK3 couples SG partitioning with mTORC1 regulation. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
AKT | down-regulates activity
phosphorylation
|
AKT1S1 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-236929 |
Thr246 |
LPRPRLNtSDFQKLK |
Homo sapiens |
HEK-293 Cell |
pmid |
sentence |
12524439 |
Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40 |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
Pathways: | MTOR Signaling |
+ |
AKT1 | down-regulates activity
phosphorylation
|
AKT1S1 |
0.781 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-252544 |
Thr246 |
LPRPRLNtSDFQKLK |
Homo sapiens |
HEK-293 Cell |
pmid |
sentence |
12524439 |
Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40 |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
AKT2 | down-regulates activity
phosphorylation
|
AKT1S1 |
0.673 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-248046 |
Thr246 |
LPRPRLNtSDFQKLK |
Homo sapiens |
HEK-293 Cell |
pmid |
sentence |
12524439 |
1) PRAS40 was phosphorylated in vitro by purified Akt on the same site that was phosphorylated in insulin-treated cells; 2) activation of an inducible Akt was alone sufficient to stimulate the phosphorylation of PRAS40; and 3) cells lacking Akt1 and Akt2 exhibit a diminished ability to phosphorylate this protein |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
AKT2 | down-regulates
phosphorylation
|
AKT1S1 |
0.673 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-153931 |
|
|
Homo sapiens |
|
pmid |
sentence |
17386266 |
Insulin-stimulated phosphorylation of pras40 by akt/pkb suppresses its mtorc1 inhibitory activity. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-152936 |
|
|
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. |
|
Publications: |
2 |
Organism: |
Homo Sapiens |
+ |
14-3-3 | down-regulates
binding
|
AKT1S1 |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-162003 |
|
|
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 |
+ |
DYRK3 | down-regulates
phosphorylation
|
AKT1S1 |
0.339 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-201002 |
|
|
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 |
+ |
AKT1S1 | form complex
binding
|
mTORC1 |
0.801 |
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 |