Relation Results

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-265874	Ser113	AEDAEGQsPLSQKYS	Homo sapiens	U2-OS Cell
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-265875	Ser120	SPLSQKYsPSTEKCL	Homo sapiens	U2-OS Cell
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

Identifier	Residue	Sequence
SIGNOR-275541	Ser1174	SETSSVVsGSEMSGK
pmid	sentence
29925953	Human ELP1 S1174 phosphorylation was triggered by insulin treatment, as shown by the specific phosphorylated (p)ELP1 (S1174) antibody, and addition of a phosphorylation-mutant variant of the ELP1 protein (ELP1(S1174A)) to ELP1-depleted BRAFV600E melanoma cells failed to rescue cell survival \|In line with these findings, mTORC2 activity, but not mTORC1, was required for the insulin-induced phosphorylation of Elp1 S1174

Publications:

1

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-262535	Ser1261	PMKKLHVsTINLQKA	Mus musculus	MEF Cell
pmid	sentence
31186373	AMPK directly activates mTORC2 to promote cell survival during acute energetic stress. AMPK associates with and phosphorylates mTOR within mTORC2., these data indicate that AMPK phosphorylates mTOR on Ser1261 within mTORC2, an event that correlates with increased mTORC2 autophosphorylation and downstream signaling.

Publications:

1

Organism:

Mus Musculus

Pathways:

Acute Myeloid Leukemia, IDH-TET in AML, FLT3-ITD signaling, Leptin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-201595	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

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-255310	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-248270	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

Pathways:

MTOR Signaling

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
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
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
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

Identifier	Residue	Sequence	Organism
SIGNOR-137251	Ser2448	RSRTRTDsYSAGQSV	Homo sapiens
pmid	sentence
15905173	Importantly, phosphorylation of mTOR by S6K1 occurs at threonine 2446/serine 2448. This region has been shown previously to be part of a regulatory repressor domain. These sites are also constitutively phosphorylated in the breast cancer cell line MCF7 carrying an amplification of the S6K1 geneit has been proposed that other inputs, in addition to phosphorylation of Thr-2446/Ser-2448 by S6K1, are part of the mechanism involved in inhibiting this repressor domain

Identifier	Residue	Sequence	Organism
SIGNOR-137255	Thr2446	NKRSRTRtDSYSAGQ	Homo sapiens
pmid	sentence
15905173	Importantly, phosphorylation of mTOR by S6K1 occurs at threonine 2446/serine 2448. This region has been shown previously to be part of a regulatory repressor domain. These sites are also constitutively phosphorylated in the breast cancer cell line MCF7 carrying an amplification of the S6K1 geneit has been proposed that other inputs, in addition to phosphorylation of Thr-2446/Ser-2448 by S6K1, are part of the mechanism involved in inhibiting this repressor domain

Publications:

2

Organism:

Homo Sapiens

Pathways:

FLT3-ITD signaling, Leptin Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-251099	Ser2448	RSRTRTDsYSAGQSV	Homo sapiens
pmid	sentence
10910062	Although AKT phosphorylated mTOR at two COOH-terminal sites (Thr2446 and Ser2448) in vitro, Ser2448 was the major phosphorylation site in insulin-stimulated or -activated AKT-expressing human embryonic kidney cells. Transient transfection assays with mTOR mutants bearing Ala substitutions at Ser2448 and/or Thr2446 indicated that AKT-dependent mTOR phosphorylation was not essential for either PHAS-I phosphorylation or p70S6K activation in HEK cells.

Publications:

1

Organism:

Homo Sapiens

Pathways:

FLT3-ITD signaling, Glioblastoma Multiforme, Parkinson

Identifier	Residue	Sequence	Organism
SIGNOR-244311	Ser2448	RSRTRTDsYSAGQSV	Homo sapiens
pmid	sentence
10910062	AKT phosphorylated mTOR at two COOH-terminal sites (Thr2446 and Ser2448) in vitro, Ser2448 was the major phosphorylation site in insulin-stimulated or -activated AKT-expressing human embryonic kidney cells. These results demonstrate that mTOR is a direct target of the PI3K-AKT signaling pathway in mitogen-stimulated cells, and that the identified AKT phosphorylation sites are nested within a repressor domain that negatively regulates the catalytic activity of mTOR.¬†

Identifier	Residue	Sequence	Organism
SIGNOR-251482	Thr2446	NKRSRTRtDSYSAGQ	Homo sapiens
pmid	sentence
10910062	AKT phosphorylated mTOR at two COOH-terminal sites (Thr2446 and Ser2448) in vitro, Ser2448 was the major phosphorylation site in insulin-stimulated or -activated AKT-expressing human embryonic kidney cells. These results demonstrate that mTOR is a direct target of the PI3K-AKT signaling pathway in mitogen-stimulated cells, and that the identified AKT phosphorylation sites are nested within a repressor domain that negatively regulates the catalytic activity of mTOR.¬†

Publications:

2

Organism:

Homo Sapiens

Pathways:

Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, miRNA in AML, FLT3-ITD in AML, FLT3-ITD signaling, Glioblastoma Multiforme, Leptin Signaling, MTOR Signaling, Pancreatic ductal adenocarcinoma (PDA)

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-75394	Ser2481	TVPESIHsFIGDGLV	Homo sapiens	T-lymphocyte
pmid	sentence
10702316	We report here the identification of a FRAP autophosphorylation site. This site, Ser-2481, is located in a hydrophobic region near the conserved carboxyl-terminal FRAP tail. We demonstrate that the COOH-terminal tail is required for FRAP kinase activity and for signaling to the translational regulator p70(s6k) (ribosomal subunit S6 kinase).

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-235427	Ser2481	TVPESIHsFIGDGLV	Mus musculus	NIH-3T3 Cell
pmid	sentence
20022946	We have found that in HEK293 cells and 3T3-L1 adipocytes, insulin promotes both raptor- and rictor-associated mTOR Ser(P)-2481 in a wortmannin-sensitive manner. Thus, insulin signals via PI3K to promote both mTORC1- and mTORC2-associated mTOR Ser-2481 autophosphorylation.

Publications:

2

Organism:

Homo Sapiens, Mus Musculus

Pathways:

Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, IDH-TET in AML, KIT in AML, miRNA in AML, FLT3-ITD in AML, FLT3-ITD signaling, Glioblastoma Multiforme, Leptin Signaling, MTOR Signaling, Parkinson, Pancreatic ductal adenocarcinoma (PDA), Rett syndrome

Identifier	Residue	Sequence	Organism
SIGNOR-176849	Ser293	SSGYFSSsPTLSSSP	Homo sapiens
pmid	sentence
22017875	Our data reveal critical roles for mtor itself as well as cki in generating a degron in deptor that is recognized by _-trcp, and promotes deptor turnover by the proteasome.

Identifier	Residue	Sequence	Organism
SIGNOR-176853	Ser299	SSPTLSSsPPVLCNP	Homo sapiens
pmid	sentence
22017875	Our data reveal critical roles for mtor itself as well as cki in generating a degron in deptor that is recognized by _-trcp, and promotes deptor turnover by the proteasome.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-259813	Ser3	DQEWESPsPPKPTVF	Homo sapiens
pmid	sentence
20537536	A critical step in autophagy induction comprises the inactivation of a key negative regulator of the process, the Ser/Thr kinase mammalian target of rapamycin (mTOR). Here we identify death-associated protein 1 (DAP1) as a novel substrate of mTOR that negatively regulates autophagy. Mapping of the phosphorylation sites and analysis of phosphorylation mutants indicated that DAP1 is functionally silenced in growing cells through mTOR-dependent phosphorylations on Ser3 and Ser51.

Identifier	Residue	Sequence	Organism
SIGNOR-259812	Ser51	DQEWESPsPPKPTVF	Homo sapiens
pmid	sentence
20537536	A critical step in autophagy induction comprises the inactivation of a key negative regulator of the process, the Ser/Thr kinase mammalian target of rapamycin (mTOR). Here we identify death-associated protein 1 (DAP1) as a novel substrate of mTOR that negatively regulates autophagy. Mapping of the phosphorylation sites and analysis of phosphorylation mutants indicated that DAP1 is functionally silenced in growing cells through mTOR-dependent phosphorylations on Ser3 and Ser51.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-52700	Ser307	TRRSRTEsITATSPA	Homo sapiens
pmid	sentence
9335553	These results indicate that activation of protein kinase c stimulates a kinase which can phosphorylate insulin receptor substrate-1 at serine 612, resulting in an inhibition of insulin signaling in the cell these data suggest that: 1) activation of pkctheta contributes to ikk and jnk activation by ffas;2) ikk and jnk mediate pkctheta signals for irs-1 serine phosphorylation and degradation; ser-302 phosphorylation is dependent on pi 3-kinase/mtor, whereas ser-307 depends on c-jun nh2-terminal kinase to inhibit irs1 tyrosine phosphorylation. Ser-636 is located around the pi 3-kinase binding site and, therefore, thought to inhibit pi 3-kinase signaling.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-106570	Ser307	TRRSRTEsITATSPA	Rattus norvegicus	Fibroblast
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-106574	Ser312	TESITATsPASMVGG	Rattus norvegicus	Fibroblast
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-106578	Ser315	ITATSPAsMVGGKPG	Rattus norvegicus	Fibroblast
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism
SIGNOR-106582	Ser616	DDGYMPMsPGVAPVP	Rattus norvegicus
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism
SIGNOR-106586	Ser636	SGDYMPMsPKSVSAP	Rattus norvegicus
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-106590	Ser639	YMPMSPKsVSAPQQI	Rattus norvegicus	Fibroblast
pmid	sentence
11287630	Mtor induced the serine phosphorylation of irs-1 (ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that tnf impairs insulin signaling through irs-1 by activation of a pi 3-kinase/akt/mtor pathway, which is antagonized by pten

Publications:

7

Organism:

Homo Sapiens, Rattus Norvegicus

Tissue:

Kidney

Pathways:

Leptin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273679	Ser348	DPESNPTsPMAGRRH	Rattus norvegicus	Hepatic Stellate Cell
pmid	sentence
28112218	Binding of La ribonucleoprotein domain family, member 6 (LARP6) to collagen mRNAs regulates their translation and is necessary for high type I collagen expression. Here we show that mTORC1 phosphorylates LARP6 on S348 and S409. The S348A/S409A mutant of LARP6 acts as a dominant negative protein in collagen biosynthesis, which retards secretion of type I collagen and causes excessive posttranslational modifications.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273678	Ser409	GRLNCSTsPEIFRKC	Rattus norvegicus	Hepatic Stellate Cell
pmid	sentence
28112218	Binding of La ribonucleoprotein domain family, member 6 (LARP6) to collagen mRNAs regulates their translation and is necessary for high type I collagen expression. Here we show that mTORC1 phosphorylates LARP6 on S348 and S409. The S348A/S409A mutant of LARP6 acts as a dominant negative protein in collagen biosynthesis, which retards secretion of type I collagen and causes excessive posttranslational modifications.

Publications:

2

Organism:

Rattus Norvegicus

Identifier	Residue	Sequence	Organism
SIGNOR-250293	Ser370	TRQTPVDsPDDTALS	in vitro
pmid	sentence
11733037	In vitro phosphorylation and activation of p70β by mTOR and PDK1. replacement of Ser383 to Gly (S383G) reduced but still retained nearly half of the kinase activity of the wild-type.

Identifier	Residue	Sequence	Organism
SIGNOR-250294	Thr228	HEGAVTHtFCGTIEY	in vitro
pmid	sentence
11733037	In vitro phosphorylation and activation of p70β by mTOR and PDK1. We observed that the replacement of either Thr241 or Thr401 to Ala in p70β1(T241A, T401A) severely decreased the kinase activity.

Identifier	Residue	Sequence	Organism
SIGNOR-250295	Thr388	NQAFLGFtYVAPSVL	in vitro
pmid	sentence
11733037	In vitro phosphorylation and activation of p70β by mTOR and PDK1. We observed that the replacement of either Thr241 or Thr401 to Ala in p70β1(T241A, T401A) severely decreased the kinase activity.

Publications:

3

Organism:

In Vitro

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-101328	Ser394	TRQTPVDsPDDSTLS	Mus musculus	MEF Cell
pmid	sentence
12782654	S6K1 is a positive regulator of protein synthesis, and its activity is induced by mTOR-mediated phosphorylation.

Identifier	Residue	Sequence	Organism
SIGNOR-201530	Ser394	TRQTPVDsPDDSTLS	Sus scrofa
pmid	sentence
23486913	Collectively, 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

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-101332	Ser434	SFEPKIRsPRRFIGS	Mus musculus	MEF Cell
pmid	sentence
12782654	S6K1 is a positive regulator of protein synthesis, and its activity is induced by mTOR-mediated phosphorylation.

Identifier	Residue	Sequence	Organism
SIGNOR-201534	Ser434	SFEPKIRsPRRFIGS	Sus scrofa
pmid	sentence
23486913	Collectively, 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

Identifier	Residue	Sequence	Organism
SIGNOR-255839	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-235507	Thr412	NQVFLGFtYVAPSVL	Mus musculus	NIH-3T3 Cell
pmid	sentence
17510057	mTORC1 catalyzes the phosphorylation of eIF4E binding protein-1 (4EBP1, also known as PHAS-I) and p70 S6 kinase 1 (S6K1)Phosphorylation of S6K1 at Thr-389

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-101336	Thr412	NQVFLGFtYVAPSVL	Mus musculus	MEF Cell
pmid	sentence
12782654	S6K1 is a positive regulator of protein synthesis, and its activity is induced by mTOR-mediated phosphorylation.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-72682	Thr412	NQVFLGFtYVAPSVL	Homo sapiens	HEK-293 Cell
pmid	sentence
10579915	S6 kinases are under the control of the PI3K relative, mammalian Target Of Rapamycin (mTOR), which may serve an additional function as a checkpoint for amino acid availability.

Identifier	Residue	Sequence	Organism
SIGNOR-72357	Thr412	NQVFLGFtYVAPSVL	in vitro
pmid	sentence
10567431	We report here that a mammalian recombinant p70alpha polypeptide, extracted in an inactive form from rapamycin-treated cells, can be directly phosphorylated by the mTOR kinase in vitro predominantly at the rapamycin-sensitive site Thr-412. mTOR-catalyzed p70alpha phosphorylation in vitro is accompanied by a substantial restoration in p70alpha kinase activity toward its physiologic substrate

Identifier	Residue	Sequence	Organism
SIGNOR-201538	Thr412	NQVFLGFtYVAPSVL	Sus scrofa
pmid	sentence
23486913	Collectively, 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

Publications:

10

Organism:

Mus Musculus, Sus Scrofa, Homo Sapiens, In Vitro

Tissue:

Parathyroid Hormone Secreting Cell

Pathways:

FLT3-ITD signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-181531	Ser422	AEAFLGFsYAPPTDS	Homo sapiens
pmid	sentence
18925875	Mtorc2 immunoprecipitated from wild-type, but not from mlst8- or rictor-knockout cells, phosphorylated sgk1 at ser(422)

Identifier	Residue	Sequence	Organism
SIGNOR-179113	Ser422	AEAFLGFsYAPPTDS	Homo sapiens
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:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-217869	Ser473	RPHFPQFsYSASGTA	Homo sapiens	Blood Platelet
pmid	sentence
21592956	Protein kinase B (PKB, Akt) is a Ser/Thr kinase involved in the regulation of cell survival, proliferation, and metabolism and is activated by dual phosphorylation on Thr(308) in the activation loop and Ser(473) in the hydrophobic motif. It plays a contributory role to platelet function, although little is known about its regulation. In this study, we investigated the role of the mammalian target of rapamycin complex (mTORC)-2 in Akt regulation using the recently identified small molecule ATP competitive mTOR inhibitors PP242 and Torin1.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-252599	Ser473	RPHFPQFsYSASGTA	Homo sapiens	HT-29 Cell, A-549 Cell
pmid	sentence
15718470	The rictor-mtor complex directly phosphorylated akt/pkb on ser473 in vitro and facilitated thr308 phosphorylation by pdk1

Identifier	Residue	Sequence	Organism
SIGNOR-170604	Ser473	RPHFPQFsYSASGTA	Homo sapiens
pmid	sentence
21157483	Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt.Recent findings have revealed novel important roles for mTORC2 in the phosphorylation of AGC kinase family members. mTORC2 phosphorylates and activates Akt, SGK, and PKC, which regulate cell survival, cell cycle progression and anabolism

Publications:

3

Organism:

Homo Sapiens

Pathways:

FLT3-ITD signaling, Glioblastoma Multiforme, Parkinson

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-134185	Ser473	RPHFPQFsYSASGTA	Homo sapiens	HT-29 Cell, A-549 Cell
pmid	sentence
15718470	The rictor-mtor complex directly phosphorylated akt/pkb on ser473 in vitro and facilitated thr308 phosphorylation by pdk1

Identifier	Residue	Organism	Cell Line
SIGNOR-244417		Homo sapiens	Blood Platelet
pmid	sentence
21592956	Protein kinase B (PKB, Akt) is a Ser/Thr kinase involved in the regulation of cell survival, proliferation, and metabolism and is activated by dual phosphorylation on Thr(308) in the activation loop and Ser(473) in the hydrophobic motif. It plays a contributory role to platelet function, although little is known about its regulation. In this study, we investigated the role of the mammalian target of rapamycin complex (mTORC)-2 in Akt regulation using the recently identified small molecule ATP competitive mTOR inhibitors PP242 and Torin1.

Publications:

2

Organism:

Homo Sapiens

Pathways:

Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, miRNA in AML, FLT3-ITD in AML, FLT3-ITD signaling, Glioblastoma Multiforme, Leptin Signaling, MTOR Signaling, Pancreatic ductal adenocarcinoma (PDA)

Identifier	Residue	Sequence
SIGNOR-272986	Ser52	KRVELPDsPRSTFLL
pmid	sentence
23524951	We show that under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated. In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. As ULK1 has been shown to activate AMBRA1 by phosphorylation, the proposed pathway may act as a positive regulation loop, which may be targeted in human disorders linked to impaired autophagy.\|mTOR phosphorylates AMBRA1 at Ser 52, inhibiting its role in ULK1 modification

Publications:

1

Identifier	Residue	Sequence	Organism
SIGNOR-165791	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
SIGNOR-165795	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
SIGNOR-164348	Ser68	PPQTSGLsPSRLSKS	Homo sapiens
pmid	sentence
20233713	The identification of maf1 as an mtor-regulated phosphoprotein implicates mtor in the broader regulatory mechanisms governing pol iii activity in cancer cells.

Identifier	Residue	Sequence	Organism
SIGNOR-164352	Ser75	SPSRLSKsQGGEEEG	Homo sapiens
pmid	sentence
20233713	Employing an mtor active-site inhibitor wye-125132 (wye-132), we have performed quantitative phospho-proteomics and identified a ser-75-containing phosphopeptide from maf1, a known repressor of rna polymerase iii (pol iii) transcriptionmaf1 mutant proteins carrying s75a alone or with s60a, t64a, and s68a (maf1-s75a, maf1-4a) progressively enhanced basal repression of trna in actively proliferating cells and attenuated amino acid-induced trna transcription

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-166054	Ser75	SPSRLSKsQGGEEEG	Homo sapiens	HeLa Cell
pmid	sentence
20543138	Maf1, a repressor that binds and inhibits pol iii, is phosphorylated in a mtor-dependent manner both in vitro and in vivo at serine 75

Identifier	Residue	Sequence	Organism
SIGNOR-165799	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:

6

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-275430	Ser616	PIPIMPAsPQKGHAV	Homo sapiens	JURKAT Cell
pmid	sentence
34535949	Furthermore, we confirmed also in Jurkat cells that the specific silencing of both ERK1/2 and mTOR by siRNA downregulates Drp1 phosphorylation on Ser616

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-101115	Ser65	FLMECRNsPVTKTPP	Homo sapiens	HEK-293 Cell
pmid	sentence
12747827	Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BPs efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-219257	Ser65	FLMECRNsPVTKTPP	Sus scrofa	Trophectoderm
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-226714	Ser65	FLMECRNsPVTKTPP	Homo sapiens	HEK-293T Cell
pmid	sentence
10942774	PHAS-I in adipocytes and HEK293 cells is phosphorylated in the following five sites, all of which conform to a (S/T)P motif (9, 10): Thr-36, Thr-45, Ser-64, Thr-69, and Ser-82. Thr-45 and Ser-64 flank the eIF4E-binding motif (7, 8), and phosphorylation of either site blocks eIF4E binding in vitro (10, 11). Insulin stimulates the phosphorylation of Thr-36, Thr-45, Ser-64, and Thr-69 in both fat cells and HEK293 cells, and incubating cells with rapamycin decreases the phosphorylation of these sites.Immunoprecipitated epitope-tagged mammalian target of rapamycin (mTOR) phosphorylated Thr-36/45. mTOR also phosphorylated Thr-69 and Ser-64 but only when purified immune complexes were incubated with the activating antibody, mTAb1.

Identifier	Residue	Sequence	Organism
SIGNOR-250292	Ser83	PTIPGVTsPSSDEPP	Homo sapiens
pmid	sentence
9204908	MTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-55697	Thr36	LPPGDYStTPGGTLF	Homo sapiens	HEK-293 Cell
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-167180	Thr36	LPPGDYStTPGGTLF	Mus musculus	MEF Cell
pmid	sentence
20670887	Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal 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
SIGNOR-154810	Thr36	LPPGDYStTPGGTLF	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.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-101119	Thr37	PPGDYSTtPGGTLFS	Homo sapiens	HEK-293 Cell
pmid	sentence
12747827	Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BPs efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-219262	Thr37	PPGDYSTtPGGTLFS	Sus scrofa	Trophectoderm
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-55701	Thr45	PGGTLFStTPGGTRI	Homo sapiens	HEK-293 Cell
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-154814	Thr45	PGGTLFStTPGGTRI	Homo sapiens	HEK-293 Cell, Adipocyte
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-167184	Thr45	PGGTLFStTPGGTRI	Mus musculus	MEF Cell
pmid	sentence
20670887	Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal 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-219266	Thr46	GGTLFSTtPGGTRII	Sus scrofa	Trophectoderm
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-101123	Thr46	GGTLFSTtPGGTRII	Homo sapiens	HEK-293 Cell
pmid	sentence
12747827	Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BPs efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-101127	Thr70	RNSPVTKtPPRDLPT	Homo sapiens	HEK-293 Cell
pmid	sentence
12747827	Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BPs efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-226710	Thr70	RNSPVTKtPPRDLPT	Homo sapiens	HEK-293T Cell
pmid	sentence
10942774	PHAS-I in adipocytes and HEK293 cells is phosphorylated in the following five sites, all of which conform to a (S/T)P motif (9, 10): Thr-36, Thr-45, Ser-64, Thr-69, and Ser-82. Thr-45 and Ser-64 flank the eIF4E-binding motif (7, 8), and phosphorylation of either site blocks eIF4E binding in vitro (10, 11). Insulin stimulates the phosphorylation of Thr-36, Thr-45, Ser-64, and Thr-69 in both fat cells and HEK293 cells, and incubating cells with rapamycin decreases the phosphorylation of these sites.Immunoprecipitated epitope-tagged mammalian target of rapamycin (mTOR) phosphorylated Thr-36/45. mTOR also phosphorylated Thr-69 and Ser-64 but only when purified immune complexes were incubated with the activating antibody, mTAb1.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-219273	Thr70	RNSPVTKtPPRDLPT	Sus scrofa	Trophectoderm
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
SIGNOR-80797	Thr70	RNSPVTKtPPRDLPT	Homo sapiens
pmid	sentence
10942774	Mammalian target of rapamycin-dependent phosphorylation of phas-i in four (s/t)p sites detected by phospho-specific antibodies.

Publications:

18

Organism:

Homo Sapiens, Sus Scrofa, Mus Musculus

Pathways:

MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-161439	Ser727	NTIDLPMsPRTLDSL	Homo sapiens
pmid	sentence
18691976	Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-146915	Ser727	NTIDLPMsPRTLDSL	Homo sapiens	Glioblastoma Cell
pmid	sentence
16740698	Serine phosphorylation and maximal activation of stat3 during cntf signaling is mediated by the rapamycin target mtor. / a stat3 peptide was efficiently phosphorylated on ser727 in a cntf-dependent manner by mtor

Publications:

2

Organism:

Homo Sapiens

Pathways:

Acute Myeloid Leukemia, KIT in AML, FLT3-ITD signaling, Leptin Signaling, Pancreatic ductal adenocarcinoma (PDA)

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-172541	Ser758	PVVFTVGsPPSGSTP	Homo sapiens	U2-OS Cell
pmid	sentence
21383122	When cells are replenished with rich medium, mtor is activated;it phosphorylates serine 638 and serine 758. The phosphorylation of ulk1 at serine 758 then leads to reassociation between ulk1 and ampk.

Identifier	Residue	Organism
SIGNOR-187611		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.

Identifier	Residue	Organism	Cell Line
SIGNOR-183903		Homo sapiens	HEK-293 Cell
pmid	sentence
21460634	mTORC1, which is often referred to as the gatekeeper to autophagy, is a key regulator of the Ulk1-Atg13-FIP200 kinase complex.11,14,25 Under nutrient-rich conditions, active mTORC1 associates with and inactivates the Ulk1-Atg13-FIP200 complex by phosphorylating Ulk1 and Atg13.

Publications:

3

Organism:

Homo Sapiens

Pathways:

MTOR Signaling

Identifier	Residue	Sequence
SIGNOR-272086	Ser759	SSSQRAAsLDSVATS
pmid	sentence
25998128	AMOTL2 is phosphorylated at serine 760 by mTORC2. Mutation of AMOTL2 mimicking constitutive Ser(760) phosphorylation blocks its ability to bind and repress YAP leading to increased relative expression of known YAP gene targets.

Publications:

1

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-174882	Ser855	QRVLDTSsLTQSAPA	Homo sapiens	HEK-293 Cell
pmid	sentence
19864431	Strikingly, raptor Ser(863) phosphorylation is absolutely required for raptor Ser(859) and Ser(855) phosphorylation. These data suggest that mTORC1 activation leads to raptor multisite phosphorylation and that raptor Ser(863) phosphorylation functions as a master biochemical switch that modulates hierarchical raptor phosphorylation (e.g. on Ser(859) and Ser(855))

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-184959	Ser859	DTSSLTQsAPASPTN	Homo sapiens	HEK-293 Cell
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-188920	Ser859	DTSSLTQsAPASPTN	Homo sapiens	HEK-293 Cell
pmid	sentence
19864431	Strikingly, raptor Ser(863) phosphorylation is absolutely required for raptor Ser(859) and Ser(855) phosphorylation. These data suggest that mTORC1 activation leads to raptor multisite phosphorylation and that raptor Ser(863) phosphorylation functions as a master biochemical switch that modulates hierarchical raptor phosphorylation (e.g. on Ser(859) and Ser(855))

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-188924	Ser863	LTQSAPAsPTNKGVH	Homo sapiens	HEK-293 Cell
pmid	sentence
19864431	Our data that insulin-stimulated raptor ser863 phosphorylation requires kinase-active mtorc1 and displays rapamycin sensitivity in intact cells, together with the data of wang et al. (67) that mtor phosphorylates raptor ser863 in vitro, strongly suggest that mtor itself mediates raptor ser863 phosphorylation. / strikingly, raptor ser863 phosphorylation is absolutely required for raptor ser859 and ser855 phosphorylation. These data suggest that mtorc1 activation leads to raptor multisite phosphorylation and that raptor ser863 phosphorylation functions as a master biochemical switch that modulates hierarchical raptor phosphorylation

Publications:

4

Organism:

Homo Sapiens

Pathways:

MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-102051	Thr2446	NKRSRTRtDSYSAGQ	Homo sapiens
pmid	sentence
15905173	Importantly, phosphorylation of mTOR by S6K1 occurs at threonine 2446/serine 2448. This region has been shown previously to be part of a regulatory repressor domain. These sites are also constitutively phosphorylated in the breast cancer cell line MCF7 carrying an amplification of the S6K1 geneit has been proposed that other inputs, in addition to phosphorylation of Thr-2446/Ser-2448 by S6K1, are part of the mechanism involved in inhibiting this repressor domain

Publications:

1

Organism:

Homo Sapiens

Pathways:

FLT3-ITD signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-255841	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:

FLT3-ITD signaling, Leptin Signaling

Identifier	Residue	Organism	Cell Line
SIGNOR-93130		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. Here, we show that hamartin and tuberin function together to inhibit mammalian target of rapamycin (mtor)-mediated signaling to eukaryotic initiation factor 4e-binding protein 1 (4e-bp1) and ribosomal protein s6 kinase 1 (s6k1).

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-162006		Homo sapiens	HEK-293 Cell
pmid	sentence
20006481	Rheb stimulates the phosphorylation of mtor and plays an essential role in regulation of s6k and 4ebp1 in response to nutrients and cellular energy status.

Identifier	Residue	Organism	Cell Line
SIGNOR-135770		Homo sapiens	HEK-293 Cell
pmid	sentence
15854902	Rheb binds and regulates the mTOR kinase.

Publications:

2

Organism:

Homo Sapiens

Pathways:

MTOR Signaling

Identifier	Residue	Organism
SIGNOR-191564		Homo sapiens
pmid	sentence
22179044	In differentiated myofibres, we observed that wnt7a binding to fzd7 directly activates the akt/mtor growth pathway, thereby inducing myofibre hypertrophy.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Muscle, Skeletal Muscle, Myotube

Identifier	Residue	Organism
SIGNOR-192601		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-101324		Homo sapiens
pmid	sentence
12782654	It was shown recently that akt activates mtor through direct phosphorylation of tsc2 the serine/threonine kinase akt is an upstream positive regulator of the mammalian target of rapamycin (mtor). However, the mechanism by which akt activates mtor is not fully understood. The known pathway by which akt activates mtor is via direct phosphorylation and tuberous sclerosis complex 2 (tsc2), which is a negative regulator of mtor.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Muscle, Skeletal Muscle

Identifier	Residue	Organism
SIGNOR-255944		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.

Identifier	Residue	Organism
SIGNOR-255108		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

Publications:

2

Organism:

Homo Sapiens

Tissue:

HEK-293 Cell, Skeletal Muscle

Pathways:

Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, IDH-TET in AML, KIT in AML, miRNA in AML, FLT3-ITD in AML, FLT3-ITD signaling, Glioblastoma Multiforme, Leptin Signaling, Pancreatic ductal adenocarcinoma (PDA)

Identifier	Residue	Organism	Cell Line
SIGNOR-228657		Homo sapiens	HEK-293 Cell
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 Signaling

Identifier	Residue	Organism
SIGNOR-258268		in vitro
pmid	sentence
22037378	Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. \| The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here.

Publications:

1

Organism:

In Vitro

Identifier	Residue	Organism
SIGNOR-198242		Homo sapiens
pmid	sentence
22790199	Rag gtpases, together with a multi-protein complex called ragulator, mediate amino acid-mediated mtor recruitment to the lysosome surface where mtor becomes activated.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-245105		Homo sapiens	HEK-293 Cell
pmid	sentence
26787466	The PtdIns3-phosphatase MTMR3 interacts with mTORC1 and suppresses its activity.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-201541		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.

Identifier	Residue	Organism
SIGNOR-154821		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:

2

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-199258		Homo sapiens
pmid	sentence
23100465	Here, we show that cancer cells acquire resistance to astori by downregulating eukaryotic translation initiation factor (eif4e)-binding proteins (4e-bps-eif4ebp1, eif4ebp2).

Identifier	Residue	Organism
SIGNOR-122014		Homo sapiens
pmid	sentence
14967450	Here, we show that cancer cells acquire resistance to astori by downregulating eukaryotic translation initiation factor (eif4e)-binding proteins (4e-bps-eif4ebp1, eif4ebp2).

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-265771
pmid	sentence
29789464	The mTOR complexes are essential to neurogenesis and the establishment of neural circuits. \| Activation of mTOR complexes exerts profound effects on all the processes of neurogenesis, including dendrite formation.

Publications:

1

Pathways:

Rett syndrome

Identifier	Residue	Organism
SIGNOR-261074		Homo sapiens
pmid	sentence
7566123	Consistent with an essential role for FRAP kinase activity in vivo, autophosphorylation of FRAP is inhibited by FKBP12-rapamycin.

Publications:

1

Organism:

Homo Sapiens

Pathways:

FLT3-ITD signaling

Identifier	Residue	Organism
SIGNOR-183961		Homo sapiens
pmid	sentence
19211836	Mtor phosphorylates a mammalian homologue of atg13 and the mammalian atg1 homologues ulk1 and ulk2

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-166186		Homo sapiens
pmid	sentence
20554235	Deforolimus was well tolerated on the schedule tested in this trial with toxicity and pharmacokinetic profiles that were similar to that of other mtor inhibitors.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Muscle

Identifier	Residue	Organism
SIGNOR-183965		Homo sapiens
pmid	sentence
19211837	Mtor phosphorylates a mammalian homologue of atg13 and the mammalian atg1 homologues ulk1 and ulk2.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-255803		Homo sapiens
pmid	sentence
26055960	Our results suggest that activating mutation of FLT3 in AML can lead, to increased expression of miR-155, which then causes down-regulation of SPI1 and CEBPB and consequently causes block of myeloid differentiation.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Acute Myeloid Leukemia, miRNA in AML

Identifier	Residue	Organism
SIGNOR-179483		Homo sapiens
pmid	sentence
18636076	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. autophagy is negatively regulated by the mammalian target of rapamycin (mtor) and can be induced in all mammalian cell types by the mtor inhibitor rapamycin.

Identifier	Residue	Organism
SIGNOR-174886		Homo sapiens
pmid	sentence
21757781	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 ta rget of rapamycin (mtor) kinase. autophagy is negatively regulated by the mammalian target of rapamycin (mtor) and can be induced in all mammalian cell types by the mtor inhibitor rapamycin.

Identifier	Residue	Organism
SIGNOR-153608		Homo sapiens
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. autophagy is negatively regulated by the mammalian target of rapamycin (mtor) and can be induced in all mammalian cell types by the mtor inhibitor rapamycin.

Publications:

3

Organism:

Homo Sapiens

Pathways:

FLT3-ITD signaling

Identifier	Residue	Organism
SIGNOR-190215		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-199120		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-198245		Homo sapiens
pmid	sentence
22790199	Rag gtpases, together with a multi-protein complex called ragulator, mediate amino acid-mediated mtor recruitment to the lysosome surface where mtor becomes activated.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	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

Identifier	Residue	Organism	Cell Line
SIGNOR-167402		Homo sapiens	Melanoma Cell
pmid	sentence
20689758	M14, m288, and skmel28 (sensitive and resistant) were exposed to rad001, an mtor inhibitor, and to ly294002, a pi3k inhibitor.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-159013		Homo sapiens
pmid	sentence
17991864	Fkbp38 binds to mtor and inhibits its activity in a manner similar to that of the fkbp12-rapamycin complex.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-207869		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-266703		Homo sapiens	HEK-293 Cell
pmid	sentence
29125601	TM9SF4 inhibited mTOR activity in HEK293 cells. Under nutrient starvation, TM9SF4 functions to facilitate mTOR inactivation, resulting in an enhanced autophagic flux, which serves to protect cells from apoptotic cell death.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-174071		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

Pathways:

Acute Myeloid Leukemia, FLT3 in AML, FLT3-ITD signaling

Identifier	Residue	Organism	Cell Line
SIGNOR-93133		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

Identifier	Residue	Organism
SIGNOR-207818		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
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)

Identifier	Residue	Organism
SIGNOR-205986		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-201499		Homo sapiens
pmid	sentence
23436801	Torin2, a second generation atp-competitive inhibitor that is potent and selective for mtor..

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-206289		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-206313		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-207788		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-192693		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-255107		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:

FLT3-ITD signaling, Glioblastoma Multiforme, Parkinson

Identifier	Residue	Organism
SIGNOR-207809		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-207800		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-244314		Homo sapiens
pmid	sentence
12782654	It was shown recently that akt activates mtor through direct phosphorylation of tsc2 the serine/threonine kinase akt is an upstream positive regulator of the mammalian target of rapamycin (mtor). However, the mechanism by which akt activates mtor is not fully understood. The known pathway by which akt activates mtor is via direct phosphorylation and tuberous sclerosis complex 2 (tsc2), which is a negative regulator of mtor.

Publications:

1

Organism:

Homo Sapiens

Tissue:

Muscle, Skeletal Muscle

Pathways:

Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, miRNA in AML, FLT3-ITD in AML, FLT3-ITD signaling, Glioblastoma Multiforme, Leptin Signaling, MTOR Signaling, Pancreatic ductal adenocarcinoma (PDA)

Identifier	Residue	Organism
SIGNOR-252705		Homo sapiens
pmid	sentence
18721898	Phosphoinositide 3-kinase (pi3k)-dependent activation of the rheb-mtor pathway triggers the simultaneous local synthesis of tc10 and par3.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, FLT3-ITD in AML, FLT3-ITD signaling, Leptin Signaling, Pancreatic ductal adenocarcinoma (PDA)

Identifier	Residue	Organism
SIGNOR-260096		Homo sapiens
pmid	sentence
30274374	AMPK inhibits the mTOR pathway through phosphorylation and activation of tuberous sclerosis protein 2 (TSC2) and causes direct activation of unc-51-like autophagy activating kinase 1 (ULK1) via phosphorylation of Ser555, thus promoting initiation of autophagy.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Acute Myeloid Leukemia, IDH-TET in AML, FLT3-ITD signaling, Leptin Signaling, MTOR Signaling

Identifier	Residue	Organism	Cell Line
SIGNOR-253554		Homo sapiens	A-549 Cell, 1205-Lu Cell
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

Identifier	Residue	Organism
SIGNOR-168188		Homo sapiens
pmid	sentence
20884880	Sgk-1 activation in response to stretch is blocked by insulin-like growth factor (igf)-1 receptor inhibitor and mammalian target of rapamycin complex (mtorc)2 inhibitor (ku-0063794) but not mtorc1 inhibitor (rapamycin).

Publications:

1

Organism:

Homo Sapiens

Tissue:

Muscle, Smooth Muscle

Identifier	Residue	Organism
SIGNOR-122035		Homo sapiens
pmid	sentence
14967450	While promoting initiation of protein translation through mtor, eukaryoticinitiation factor 4e, and the ribosomal p70-s6 kinase.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-190937		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-169712		Homo sapiens
pmid	sentence
21081844	Temsirolimus, an inhibitor of mammalian target of rapamycin (mtor) complex 1, is approved for the treatment of metastatic renal cell carcinoma (rcc).

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-76562		Homo sapiens
pmid	sentence
10753870	Abl binds directly to raft1 and phosphorylates raft1 in vitro and in vivo. c-abl inhibits autophosphorylation of raft1 and raft1-mediated phosphorylation p70(s6k).

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-180453		Homo sapiens
pmid	sentence
18721898	Phosphoinositide 3-kinase (pi3k)-dependent activation of the rheb-mtor pathway triggers the simultaneous local synthesis of tc10 and par3.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Glioblastoma Multiforme, MTOR Signaling

Identifier	Residue	Organism
SIGNOR-262534		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:

FLT3-ITD signaling, MTOR Signaling

Identifier	Residue	Organism
SIGNOR-112379		Homo sapiens
pmid	sentence
11729323	Pa directly interacted with the domain in mtor that is targeted by rapamycin, and this interaction was positively correlated with mtor's ability to activate downstream effectors.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-251657		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

Name	MTOR View Modifications
Full Name	Serine/threonine-protein kinase mTOR
Synonyms	FK506-binding protein 12-rapamycin complex-associated protein 1, FKBP12-rapamycin complex-associated protein, Mammalian target of rapamycin, mTOR, Mechanistic target of rapamycin, Rapamycin and FKBP12 target 1, Rapamycin target protein 1 \| FRAP, FRAP1, FRAP2, RAFT1, RAPT1
Primary ID	P42345
Links	- -
Type	protein
Relations	148
Pathways	Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, IDH-TET in AML, KIT in AML, miRNA in AML, FLT3-ITD in AML, FLT3-ITD signaling, Leptin Signaling, Mitochondrial dynamics in T cell exhaustion, MTOR Signaling, Parkinson, Rett syndrome
Inhibitors	1-[4-[[2-(2-amino-5-pyrimidinyl)-7-methyl-4-(4-morpholinyl)-6-thieno[3,2-d]pyrimidinyl]methyl]-1-piperazinyl]-2-hydroxy-1-propanone; torkinib; sirolimus; AP 23573; AZD-8055; Palomid 529; everolimus; XL765; WYE-687; PKI-587; torin 2; PP121; WAY-600; GSK1059615; 4-[6-[4-(methoxycarbonylamino)phenyl]-4-(4-morpholinyl)-1-pyrazolo[3,4-d]pyrimidinyl]-1-piperidinecarboxylic acid methyl ester; 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-pyrazolo[3,4-d]pyrimidinyl]phenyl]-3-methylurea; Ku-0063794; CH5132799; Temsirolimus
Function	Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18925875, PubMed:18497260, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (By similarity). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:12150925, PubMed:12087098, PubMed:18925875). This also includes mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3

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