Relation Results

Identifier	Residue	Sequence	Organism
SIGNOR-127904	Ser1101	GCRRRHSsETFSSTP	Mus musculus
pmid	sentence
15306821	Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulates insulin.

Identifier	Residue	Sequence	Organism
SIGNOR-51216	Ser270	EFRPRSKsQSSSNCS	Homo sapiens
pmid	sentence
9312143	Turnover of the active fraction of irs1 involves raptor-mtor- and s6k1-dependent serine phosphorylation in cell culture models of tuberous sclerosiss6k1 phosphorylates irs1 in vitro on multiple residues showing strong preference for rxrxxs/t over s/t,p sites.

Identifier	Residue	Sequence	Organism
SIGNOR-127908	Ser307	TRRSRTEsITATSPA	Mus musculus
pmid	sentence
15306821	Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-148903	Ser527	RFRKRTHsAGTSPTI	Homo sapiens	HEK-293 Cell
pmid	sentence
16914728	Turnover of the active fraction of irs1 involves raptor-mtor- and s6k1-dependent serine phosphorylation in cell culture models of tuberous sclerosiss6k1 phosphorylates irs1 in vitro on multiple residues showing strong preference for rxrxxs/t over s/t,p sites.

Identifier	Residue	Sequence	Organism
SIGNOR-127912	Ser636	SGDYMPMsPKSVSAP	Mus musculus
pmid	sentence
15306821	Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin.

Identifier	Residue	Sequence	Organism
SIGNOR-127203	Ser639	YMPMSPKsVSAPQQI	Mus musculus
pmid	sentence
15306821	Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin.

Publications:

6

Organism:

Mus Musculus, Homo Sapiens

Tissue:

Ovary, Myotube, Brain

Pathways:

Insulin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-178590	Ser145	IERIRMDsIGSTVSS	Homo sapiens
pmid	sentence
18451027	Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway, which in turn promotes the transcriptional activity of myc.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-186951	Ser15	FSLLRGPsWDPFRDW	Homo sapiens
pmid	sentence
19593530	Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk.

Identifier	Residue	Sequence	Organism
SIGNOR-186955	Ser78	PAYSRALsRQLSSGV	Homo sapiens
pmid	sentence
19593530	Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk.

Identifier	Residue	Sequence	Organism
SIGNOR-186959	Ser82	RALSRQLsSGVSEIR	Homo sapiens
pmid	sentence
19593530	Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk.

Publications:

3

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-34117	Ser167	GGRERLAsTNDKGSM	Homo sapiens
pmid	sentence
7838153	Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-267443	Ser1859	PPRIHRAsDPGLPAE	Homo sapiens	HEK-293T Cell
pmid	sentence
23429703	CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Nucleotide Biosynthesis

Identifier	Residue	Sequence	Organism
SIGNOR-201117	Ser1859	PPRIHRAsDPGLPAE	Homo sapiens
pmid	sentence
23429703	Mtorc1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein s6 kinase 1 (s6k1), which directly phosphorylates s1859 on cad, the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. Growth signaling through mtorc1 thus stimulates the production of new nucleotides to accommodate an increase in rna and dna synthesis.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Nucleotide Biosynthesis

Identifier	Residue	Sequence	Organism
SIGNOR-135172	Ser235	IAKRRRLsSLRASTS	Mus musculus
pmid	sentence
15809305	A knockin mouse carrying mutations at all phosphorylation sites in the primary s6k substrate, ribosomal protein s6 (rps6), has provided insight into the physiological role of this protein phosphorylation event. Of the many known substrates of s6k1, it is rps6 that has been shown to be directly involved, via its phosphorylation, in controlling cell size.

Identifier	Residue	Sequence	Organism
SIGNOR-135176	Ser236	AKRRRLSsLRASTSK	Mus musculus
pmid	sentence
15809305	A knockin mouse carrying mutations at all phosphorylation sites in the primary s6k substrate, ribosomal protein s6 (rps6), has provided insight into the physiological role of this protein phosphorylation event. Of the many known substrates of s6k1, it is rps6 that has been shown to be directly involved, via its phosphorylation, in controlling cell size.

Publications:

2

Organism:

Mus Musculus

Pathways:

MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-184926	Ser260	GSRVRVDsTAKVAEI	Homo sapiens
pmid	sentence
19332537	Mass spectrometry and mutagenesis analysis revealed that rsk and s6k1 phosphorylate cct_ ser-260 in vitro and in intact cells

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-274065	Ser283	ILSLRSCsLGSLGAL	in vitro
pmid	sentence
27407113	We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells.

Identifier	Residue	Sequence	Organism
SIGNOR-274068	Ser286	LRSCSLGsLGALGPA	in vitro
pmid	sentence
27407113	We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells.

Publications:

2

Organism:

In Vitro

Identifier	Residue	Sequence	Organism
SIGNOR-176858	Ser286	SSMSSCGsSGYFSSS	Homo sapiens
pmid	sentence
22017876	Deptor is phosphorylated by s6k1 and rsk1 on the degron serine residues upon serum stimulation s6k1/rsk1 and _trcp are required for ubiquitination and degradation of endogenous deptor upon mitogen stimulation.

Identifier	Residue	Sequence	Organism
SIGNOR-176862	Ser287	SMSSCGSsGYFSSSP	Homo sapiens
pmid	sentence
22017876	Deptor is phosphorylated by s6k1 and rsk1 on the degron serine residues upon serum stimulation s6k1/rsk1 and _trcp are required for ubiquitination and degradation of endogenous deptor upon mitogen stimulation.

Identifier	Residue	Sequence	Organism
SIGNOR-176866	Ser291	CGSSGYFsSSPTLSS	Homo sapiens
pmid	sentence
22017876	Deptor is phosphorylated by s6k1 and rsk1 on the degron serine residues upon serum stimulation s6k1/rsk1 and _trcp are required for ubiquitination and degradation of endogenous deptor upon mitogen stimulation.

Publications:

3

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-277256	Ser36	ARRAFRVsPPLTTGP	in vitro
pmid	sentence
27365393	Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process.

Publications:

1

Organism:

In Vitro

Identifier	Residue	Sequence	Organism
SIGNOR-109712	Ser366	SPQVRTLsGSRPPLL	Homo sapiens
pmid	sentence
11500364	We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-262943	Ser372	AKRKRKNsTGSGHSA	Homo sapiens	HeLa Cell
pmid	sentence
17936702	Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-128495	Ser383	ELPRRVNsASSSNPP	Homo sapiens
pmid	sentence
15341740	Here we identify skar as a novel and specific binding partner and substrate of s6k1 but not s6k2. We find that serines 383 and 385 of human skar are insulin-stimulated and rapamycin-sensitive s6k1 phosphorylation sites.

Identifier	Residue	Sequence	Organism
SIGNOR-128499	Ser385	PRRVNSAsSSNPPAE	Homo sapiens
pmid	sentence
15341740	Here we identify skar as a novel and specific binding partner and substrate of s6k1 but not s6k2. We find that serines 383 and 385 of human skar are insulin-stimulated and rapamycin-sensitive s6k1 phosphorylation sites.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-50603	Ser394	TRQTPVDsPDDSTLS	Homo sapiens
pmid	sentence
9271440	Interestingly, phosphorylation at several ser/thr residues within the c-terminal autoinhibitory tail appears to either activate or inhibit s6k1, depending on the cell cycle phase. phosphorylation of those residues (featured by the thr-421/ser-424 site) during mitosis pursued by cdk1 inactivates s6k1 we then assessed the phosphorylation status of the mitosis-specific inhibitory residue of s6k1, thr-421/ser-424, which is targeted by mitotic cdk1.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-98211	Ser394	TRQTPVDsPDDSTLS	Homo sapiens	HeLa Cell
pmid	sentence
12586835	A physical interaction exists between cdc2 and s6k1, and this interaction is enhanced in mitotic cells. These results suggest that cdc2 provides a signal that triggers inactivation of s6k1 in mitosis, presumably serving to spare energy for costly mitotic processes at the expense of ribosomal protein synthesis.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-50607	Ser434	SFEPKIRsPRRFIGS	Homo sapiens	HeLa Cell
pmid	sentence
9271440	The activation of p70s6k is associated with multiple phosphorylations at two sets of sites. The first set, s411, s418, t421, and s424, reside within the autoinhibitory domain, mutations of s371 abolished kinase activity. In mitotic hela cells, when the activity of cdc2 is high, s6k1 is phosphorylated at multiple ser/thr, pro (s/tp) sites, including ser(371), ser(411), thr(421), and ser(424).

Identifier	Residue	Sequence	Organism
SIGNOR-98215	Ser434	SFEPKIRsPRRFIGS	Homo sapiens
pmid	sentence
12586835	The activation of p70s6k is associated with multiple phosphorylations at two sets of sites. The first set, s411, s418, t421, and s424, reside within the autoinhibitory domain, mutations of s371 abolished kinase activity. In mitotic hela cells, when the activity of cdc2 is high, s6k1 is phosphorylated at multiple ser/thr, pro (s/tp) sites, including ser(371), ser(411), thr(421), and ser(424).

Identifier	Residue	Sequence	Organism
SIGNOR-134654	Thr444	RFIGSPRtPVSPVKF	Homo sapiens
pmid	sentence
15774499	The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain.

Identifier	Residue	Sequence	Organism
SIGNOR-111507	Thr444	RFIGSPRtPVSPVKF	Homo sapiens
pmid	sentence
11705993	Interestingly, phosphorylation at several ser/thr residues within the c-terminal autoinhibitory tail appears to either activate or inhibit s6k1, depending on the cell cycle phase. phosphorylation of those residues (featured by the thr-421/ser-424 site) during mitosis pursued by cdk1 inactivates s6k1 we then assessed the phosphorylation status of the mitosis-specific inhibitory residue of s6k1, thr-421/ser-424, which is targeted by mitotic cdk1.

Publications:

6

Organism:

Homo Sapiens

Tissue:

Muscle, Skeletal Muscle

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
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

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	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-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-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.

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-262953	Ser403	DDSTLSEsANQVFLG	in vitro
pmid	sentence
12023960	Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation.

Identifier	Residue	Sequence	Organism
SIGNOR-262952	Ser53	EGGQLNEsMDHGGVG	in vitro
pmid	sentence
12023960	Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation.

Publications:

2

Organism:

In Vitro

Identifier	Residue	Sequence	Organism
SIGNOR-123997	Ser422	RERSRTGsESSQTGT	Homo sapiens
pmid	sentence
15071500	S6k1/s6k2 specifically phosphorylate ser422 in vitro. Substitution of ser422 with ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eif4b function.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-121984	Ser434	SFEPKIRsPRRFIGS	Homo sapiens
pmid	sentence
14967450	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Identifier	Residue	Sequence	Organism
SIGNOR-169150	Ser434	SFEPKIRsPRRFIGS	Homo sapiens
pmid	sentence
21035469	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Identifier	Residue	Sequence	Organism
SIGNOR-28796	Ser434	SFEPKIRsPRRFIGS	Homo sapiens
pmid	sentence
7545671	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-182804	Ser434	SFEPKIRsPRRFIGS	Homo sapiens	Breast Cancer Cell
pmid	sentence
19085255	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase.

Identifier	Residue	Sequence	Organism
SIGNOR-28800	Ser447	GSPRTPVsPVKFSPG	Homo sapiens
pmid	sentence
7545671	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Identifier	Residue	Sequence	Organism
SIGNOR-169154	Ser447	GSPRTPVsPVKFSPG	Homo sapiens
pmid	sentence
21035469	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-182808	Ser447	GSPRTPVsPVKFSPG	Homo sapiens	Breast Cancer Cell
pmid	sentence
19085255	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase.

Identifier	Residue	Sequence	Organism
SIGNOR-121988	Ser447	GSPRTPVsPVKFSPG	Homo sapiens
pmid	sentence
14967450	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Identifier	Residue	Sequence	Organism
SIGNOR-134658	Thr444	RFIGSPRtPVSPVKF	Homo sapiens
pmid	sentence
15774499	The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain.

Identifier	Residue	Sequence	Organism
SIGNOR-111511	Thr444	RFIGSPRtPVSPVKF	Homo sapiens
pmid	sentence
11705993	The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain.

Publications:

10

Organism:

Homo Sapiens

Tissue:

Muscle, Skeletal Muscle

Pathways:

Nucleotide Biosynthesis

Identifier	Residue	Sequence	Organism
SIGNOR-111515	Ser441	SPRRFIGsPRTPVSP	Rattus norvegicus
pmid	sentence
15774499	Thr 421/Ser 424 have been reported to be targeted by ERK1, 2 (39), JNK or p38 MAPKs (36). Interestingly, with a comparable kinetics, FSH represses ERK1, 2 constitutive phosphorylation in Sertoli cells isolated from 19-d-old rats

Identifier	Residue	Sequence	Organism
SIGNOR-134662	Thr444	RFIGSPRtPVSPVKF	Rattus norvegicus
pmid	sentence
15774499	Thr 421/Ser 424 have been reported to be targeted by ERK1, 2 (39), JNK or p38 MAPKs (36). Interestingly, with a comparable kinetics, FSH represses ERK1, 2 constitutive phosphorylation in Sertoli cells isolated from 19-d-old rats

Identifier	Residue	Organism
SIGNOR-121997		Homo sapiens
pmid	sentence
14967450	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Publications:

3

Organism:

Rattus Norvegicus, Homo Sapiens

Tissue:

Carcinoma Cell

Identifier	Residue	Sequence	Organism
SIGNOR-23757	Ser466	PVRMRRNsFTPLSSS	Homo sapiens
pmid	sentence
2846551	Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.

Identifier	Residue	Sequence	Organism
SIGNOR-49371	Ser466	PVRMRRNsFTPLSSS	Homo sapiens
pmid	sentence
9211863	Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.

Publications:

2

Organism:

Homo Sapiens

Tissue:

Heart

Identifier	Residue	Sequence	Organism
SIGNOR-180771	Ser477	NSMNKLPsVSQLINP	Homo sapiens
pmid	sentence
18769144	Atm kinase is a master switch for the delta np63 alpha phosphorylation/degradation in human head and neck squamous cell carcinoma cells upon dna damage. We previously found that the pro-apoptotic dna damaging agent, cisplatin, mediated the proteasome-dependent degradation of delta np63 alpha associated with its increased phosphorylated status. We found that delta np63 alpha is phosphorylated in the time-dependent fashion at the following positions: s385, t397 and s466, which were surrounded by recognition motifs for atm, cdk2 and p70s6k kinases, respectively

Identifier	Residue	Sequence	Organism
SIGNOR-180775	Ser560	LARLGCSsCLDYFTT	Homo sapiens
pmid	sentence
18769144	Atm kinase is a master switch for the delta np63 alpha phosphorylation/degradation in human head and neck squamous cell carcinoma cells upon dna damage. We previously found that the pro-apoptotic dna damaging agent, cisplatin, mediated the proteasome-dependent degradation of delta np63 alpha associated with its increased phosphorylated status. We found that delta np63 alpha is phosphorylated in the time-dependent fashion at the following positions: s385, t397 and s466, which were surrounded by recognition motifs for atm, cdk2 and p70s6k kinases, respectively

Identifier	Residue	Sequence	Organism
SIGNOR-180784	Thr491	PQQRNALtPTTIPDG	Homo sapiens
pmid	sentence
18769144	Atm kinase is a master switch for the delta np63 alpha phosphorylation/degradation in human head and neck squamous cell carcinoma cells upon dna damage. We previously found that the pro-apoptotic dna damaging agent, cisplatin, mediated the proteasome-dependent degradation of delta np63 alpha associated with its increased phosphorylated status. We found that delta np63 alpha is phosphorylated in the time-dependent fashion at the following positions: s385, t397 and s466, which were surrounded by recognition motifs for atm, cdk2 and p70s6k kinases, respectively

Publications:

3

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-275459	Ser494	HDRSRTVsASSTGDL	Homo sapiens	HEK-293 Cell
pmid	sentence
29153836	Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236595	Ser527	RFRKRTHsAGTSPTI	Mus musculus	MEF Cell
pmid	sentence
18498745	In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-236599	Ser639	YMPMSPKsVSAPQQI	Mus musculus	MEF Cell
pmid	sentence
18498745	In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8

Publications:

2

Organism:

Mus Musculus

Pathways:

Insulin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-273844	Ser549	VWRQRYQsHPDAAVQ	Homo sapiens
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:

1

Organism:

Homo Sapiens

Pathways:

FLT3-ITD signaling, Insulin Signaling, MTOR Signaling

Identifier	Residue	Sequence
SIGNOR-277283	Ser555	RYRRRTQsSGQDGRP
pmid	sentence
27780861	Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. These data suggest that S6K1-mediated PIPKIγ90 phosphorylation regulates cell migration and invasion by controlling PIPKIγ90 degradation.

Identifier	Residue	Sequence
SIGNOR-277282	Thr553	QPRYRRRtQSSGQDG
pmid	sentence
27780861	Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. These data suggest that S6K1-mediated PIPKIγ90 phosphorylation regulates cell migration and invasion by controlling PIPKIγ90 degradation.

Publications:

2

Identifier	Residue	Sequence	Organism
SIGNOR-150144	Ser67	KRRLRKNsSRDSGRG	Homo sapiens
pmid	sentence
17053147	Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-160989	Ser67	KRRLRKNsSRDSGRG	Homo sapiens	HEK-293 Cell
pmid	sentence
18296647	Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.

Publications:

2

Organism:

Homo Sapiens

Tissue:

Skin

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-275433	Ser83	FRAVHLHsGEELVCK	Homo sapiens	HEK-293T Cell
pmid	sentence
24089522	Furthermore, Smurf1-mediated ubiquitination required phosphorylation of TRIB2 by p70 S6 kinase (p70S6K) via another domain (amino acids 69-85) that is also essential for correct TRIB2 subcellular localization. Mutation of Ser-83 diminished p70S6K-induced phosphorylation of TRIB2.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-196756	Ser84	LTKKRALsISPLSDA	Homo sapiens
pmid	sentence
22439934	In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-161995	Thr1135	NRRIRTLtEPSVDFN	Homo sapiens
pmid	sentence
19995915	Phosphorylation of rictor on thr1135 did not affect mtorc2 assembly, kinase activity, or cellular localization. However, cells expressing a rictor t1135a mutant were found to have increased mtorc2-dependent phosphorylation of akt

Publications:

1

Organism:

Homo Sapiens

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-55306	Thr252	HDGTVTHtFCGTIEY	Homo sapiens
pmid	sentence
9445476	A regulatory link between p70s6k and pkb was demonstrated, as pdk1 was found to selectively phosphorylate p70s6k at thr229. More importantly, pdk1 activated p70s6k in vitro and in vivo, whereas the catalytically inactive pdk1 blocked insulin-induced activation of p70s6k. one of the most studied signalling events controlled by ptdins(3,4,5)p3, comprises the activation of a group of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.

Identifier	Residue	Sequence	Organism
SIGNOR-188907	Thr252	HDGTVTHtFCGTIEY	Homo sapiens
pmid	sentence
19864428	A regulatory link between p70s6k and pkb was demonstrated, as pdk1 was found to selectively phosphorylate p70s6k at thr229. More importantly, pdk1 activated p70s6k in vitro and in vivo, whereas the catalytically inactive pdk1 blocked insulin-induced activation of p70s6k. One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated. Phosphorylation and activation of p70s6k by pdk1.

Identifier	Residue	Sequence	Organism
SIGNOR-55310	Thr412	NQVFLGFtYVAPSVL	Homo sapiens
pmid	sentence
9445476	A regulatory link between p70s6k and pkb was demonstrated, as pdk1 was found to selectively phosphorylate p70s6k at thr229. More importantly, pdk1 activated p70s6k in vitro and in vivo, whereas the catalytically inactive pdk1 blocked insulin-induced activation of p70s6k. one of the most studied signalling events controlled by ptdins(3,4,5)p3, comprises the activation of a group of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.

Identifier	Residue	Sequence	Organism
SIGNOR-188911	Thr412	NQVFLGFtYVAPSVL	Homo sapiens
pmid	sentence
9445476	A regulatory link between p70s6k and pkb was demonstrated, as pdk1 was found to selectively phosphorylate p70s6k at thr229. More importantly, pdk1 activated p70s6k in vitro and in vivo, whereas the catalytically inactive pdk1 blocked insulin-induced activation of p70s6k.

Publications:

4

Organism:

Homo Sapiens

Pathways:

FLT3-ITD signaling, Insulin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-243338	Thr252	HDGTVTHtFCGTIEY	in vitro
pmid	sentence
9445476	The results presented here are consistent with PDK1 as the in vivo kinase responsible for mediating Thr252 phosphorylation in the catalytic domain of p70s6k.

Publications:

1

Organism:

In Vitro

Pathways:

FLT3-ITD signaling, Insulin Signaling, MTOR Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-237454	Thr390	DSKFTRQtPVDSPDD	Homo sapiens
pmid	sentence
21986499	Here we report the identification of ribosomal protein S6 kinase 1 (S6K1) as a novel substrate of PHLPP.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-248247	Thr390	DSKFTRQtPVDSPDD	Homo sapiens	HT-29 Cell
pmid	sentence
21986499	We show that PHLPP preferentially dephosphorylates the hydrophobic motif T389 site in S6K1 in vitro

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
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	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

Identifier	Residue	Sequence	Organism
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
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.

Identifier	Residue	Sequence	Organism
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
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.

Publications:

4

Organism:

Homo Sapiens

Pathways:

Insulin Signaling

Identifier	Residue	Sequence	Organism
SIGNOR-265944	Thr597	SQRGRADtGLETSTR	in vitro
pmid	sentence
28967905	MRE11 is highly unstable in PTEN-deficient cells but stability can be significantly restored by inhibiting mTORC1 or p70S6 kinase (p70S6K), downstream kinases whose activities are stimulated by AKT, or by mutating a residue in MRE11 that we show is phosphorylated by p70S6K in vitro.

Publications:

1

Organism:

In Vitro

Identifier	Residue	Organism
SIGNOR-165224		Homo sapiens
pmid	sentence
20444422	The human homolog of pp2a-b', ppp2r5c, also counteracts s6k1 phosphorylation, indicating a conserved mechanism in mammals

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-167190		Mus musculus	MEF Cell
pmid	sentence
20670887	We find that srebp1 and 2 promote proliferation downstream of mtorc1, and the activation of these transcription factors is mediated by s6k1.

Publications:

1

Organism:

Mus Musculus

Pathways:

Insulin Signaling, MTOR Signaling

Identifier	Residue	Organism
SIGNOR-23575		Homo sapiens
pmid	sentence
2826472	Protein phosphatase 2a inactivates the mitogen-stimulated s6 kinase from swiss mouse 3t3 cells

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-270198		Homo sapiens
pmid	sentence
14967450	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Publications:

1

Organism:

Homo Sapiens

Tissue:

Carcinoma Cell

Pathways:

FLT3-ITD signaling, Insulin Signaling, MTOR Signaling, Nucleotide Biosynthesis

Identifier	Residue	Organism
SIGNOR-277080		Homo sapiens
pmid	sentence
19436944	Expression of WT-PTEN also caused decreased activation of Akt, p70 S6K, and Erk signaling pathways.\|This may potentially be a result of PTEN inhibition of p70 S6K phosphorylation and may explain the mechanism by which PTEN inhibits proliferation of HSCs.

Publications:

1

Organism:

Homo Sapiens

Pathways:

Insulin Signaling, MTOR Signaling

Identifier	Residue	Organism
SIGNOR-201502		Homo sapiens
pmid	sentence
23436801	Torin2 inhibited mtorc1-dependent t389 phosphorylation on s6k (rps6kb1)

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-149367		Homo sapiens
pmid	sentence
17181399	Finally, downregulation of p70 s6 kinase by sirna significantly enhanced the fgf-2-stimulated vegf release and phosphorylation of sapk/jnk.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-270103		Homo sapiens
pmid	sentence
14967450	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

Publications:

1

Organism:

Homo Sapiens

Tissue:

Carcinoma Cell

Name	RPS6KB1 View Modifications
Full Name	Ribosomal protein S6 kinase beta-1
Synonyms	S6K-beta-1, S6K1, 70 kDa ribosomal protein S6 kinase 1, P70S6K1, p70-S6K 1, Ribosomal protein S6 kinase I, Serine/threonine-protein kinase 14A, p70 ribosomal S6 kinase alpha, p70 S6 kinase alpha, p70 S6K-alpha, p70 S6KA \| STK14A
Primary ID	P23443
Links	- -
Type	protein
Relations	97
Pathways	FLT3-ITD signaling, Insulin Signaling, MTOR Signaling, Nucleotide Biosynthesis, Satellite: IGF1
Function	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239).

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