Ser2448
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Home > Phosphorylation Site Page: > Ser2448  -  mTOR (mouse)

Site Information
RsRtRtDsysAGQsV   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447578

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 5 , 28 ) , mass spectrometry ( 2 , 4 , 12 , 13 , 21 , 23 , 25 , 26 , 27 , 30 ) , mutation of modification site ( 5 ) , phospho-antibody ( 3 , 5 , 6 , 7 , 8 , 9 , 10 , 15 , 16 , 17 , 18 , 22 , 24 , 28 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ) , western blotting ( 3 , 5 , 6 , 7 , 8 , 9 , 10 , 15 , 17 , 18 , 22 , 24 , 28 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 )
Disease tissue studied:
Alzheimer's disease ( 3 ) , brain cancer ( 33 ) , astrocytoma ( 33 ) , lung cancer ( 35 ) , pancreatic cancer ( 16 ) , major depressive disorder ( 15 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 12 ) , 'brain, cerebral cortex' ( 5 ) , 'brain, hippocampus' ( 15 ) , 'brain, hippocampus' [FKBP12 (mouse), homozygous knockout] ( 28 ) , 'brain, hippocampus, dentate gyrus' [FKBP12 (mouse), homozygous knockout] ( 28 ) , 'brain, nucleus accumbens' ( 6 ) , 'neuron, cortical' ( 17 , 32 ) , 32D (myeloid) [BCR-ABL1 (human), transfection] ( 22 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 39 ) , 3T3-L1 (fibroblast) ( 25 ) , astrocyte ( 33 ) , BaF3 ('B lymphocyte, precursor') ( 24 ) , BaF3 ('B lymphocyte, precursor') [JAK3 (human), transfection] ( 2 ) , BMMC (mast) ( 18 ) , brain ( 13 , 21 , 30 , 33 ) , C2C12 (myoblast) ( 26 , 27 , 31 , 34 , 36 , 38 ) , CHO (fibroblast) [Tau iso8 (human)] ( 37 ) , CT-2A (astrocyte) ( 33 ) , E14tg2a ('stem, embryonic') ( 8 ) , embryo ( 13 ) , heart ( 9 ) , liver ( 4 , 13 , 23 ) , lung ( 35 ) , macrophage-bone marrow ( 3 ) , neuron-'brain, hippocampus' ( 15 ) , oocyte ( 7 ) , pancreatic ( 16 ) , uterus ( 10 )

Upstream Regulation
Regulatory protein:
Akt1 (human) ( 24 ) , ALK (human) ( 24 ) , AMPKA1 (mouse) ( 36 ) , BDNF (human) ( 15 ) , FKBP12 (mouse) ( 28 ) , FMR1 (mouse) ( 5 ) , FOXO1A (mouse) ( 34 ) , LKB1 (mouse) ( 7 ) , NPM1 (human) ( 24 ) , RAP1B (mouse) ( 6 )
Treatments:
17-beta-estradiol ( 10 ) , 2-deoxyglucose ( 20 , 33 ) , acadesine ( 17 , 20 , 32 , 36 ) , amino_acid_starvation ( 38 ) , AS252424 ( 18 ) , benzo(a)pyrene ( 35 ) , butaprost ( 18 ) , cocaine ( 6 ) , exercise ( 9 ) , FGF2 ( 29 ) , glucose ( 20 , 36 ) , IC87114 ( 18 ) , IL-3 ( 24 ) , imatinib ( 22 , 24 ) , insulin ( 12 , 32 , 38 ) , ionizing_radiation ( 39 ) , ketamine ( 15 ) , leucine ( 36 ) , LIF withdrawal ( 8 ) , LY294002 ( 12 , 32 ) , NTCU ( 35 ) , PD184352 ( 10 ) , PGE2 ( 18 ) , PIF ( 31 ) , pomegranate_wine ( 35 ) , PTX ( 18 ) , pyruvate ( 36 ) , RAD001 ( 22 ) , rapamycin ( 10 , 18 ) , serum ( 38 ) , sulprostone ( 18 ) , tamoxifen ( 34 ) , Torin1 ( 18 ) , troglitazone ( 37 ) , wortmannin ( 3 , 18 , 38 )

Downstream Regulation
Effects of modification on mTOR:
intracellular localization ( 39 )

References 

1

Brandt C, et al. (2018) Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation. Cell 175, 1321-1335.e20
30445039   Curated Info

2

Degryse S, et al. (2017) Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia. Leukemia
28852199   Curated Info

3

Ulland TK, et al. (2017) TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease. Cell 170, 649-663.e13
28802038   Curated Info

4

Robles MS, Humphrey SJ, Mann M (2017) Phosphorylation Is a Central Mechanism for Circadian Control of Metabolism and Physiology. Cell Metab 25, 118-127
27818261   Curated Info

5

Sawicka K, et al. (2016) Elevated ERK/p90 ribosomal S6 kinase activity underlies audiogenic seizure susceptibility in fragile X mice. Proc Natl Acad Sci U S A 113, E6290-E6297
27663742   Curated Info

6

Cahill ME, et al. (2016) Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. Neuron 89, 566-82
26844834   Curated Info

7

Jiang ZZ, et al. (2016) LKB1 acts as a critical gatekeeper of ovarian primordial follicle pool. Oncotarget 7, 5738-53
26745759   Curated Info

8

Cherepkova MY, Sineva GS, Pospelov VA (2016) Leukemia inhibitory factor (LIF) withdrawal activates mTOR signaling pathway in mouse embryonic stem cells through the MEK/ERK/TSC2 pathway. Cell Death Dis 7, e2050
26775702   Curated Info

9

Sturgeon K, et al. (2015) Moderate-intensity treadmill exercise training decreases murine cardiomyocyte cross-sectional area. Physiol Rep 3
25991723   Curated Info

10

Wang Y, Zhu L, Kuokkanen S, Pollard JW (2015) Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC-ERK1/2-mTOR signaling pathway. Proc Natl Acad Sci U S A 112, E1382-91
25733860   Curated Info

11

Pagano AF, et al. (2014) Autophagy and protein turnover signaling in slow-twitch muscle during exercise. Med Sci Sports Exerc 46, 1314-25
24389528   Curated Info

12

Humphrey SJ, et al. (2013) Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2. Cell Metab 17, 1009-20
23684622   Curated Info

13

Stokes MP, et al. (2012) PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS. Mol Cell Proteomics 11, 187-201
22322096   Curated Info

14

Ryu JM, Han HJ (2011) L-threonine regulates G1/S phase transition of mouse embryonic stem cells via PI3K/Akt, MAPKs, and mTORC pathways. J Biol Chem 286, 23667-78
21550972   Curated Info

15

Autry AE, et al. (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475, 91-5
21677641   Curated Info

16

Kennedy AL, et al. (2011) Activation of the PIK3CA/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis. Mol Cell 42, 36-49
21474066   Curated Info

17

Williams T, et al. (2011) AMP-activated protein kinase (AMPK) activity is not required for neuronal development but regulates axogenesis during metabolic stress. Proc Natl Acad Sci U S A 108, 5849-54
21436046   Curated Info

18

Kuehn HS, et al. (2011) Prostaglandin E2 activates and utilizes mTORC2 as a central signaling locus for the regulation of mast cell chemotaxis and mediator release. J Biol Chem 286, 391-402
20980255   Curated Info

19

Sundaresan NR, et al. (2011) The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. Sci Signal 4, ra46
21775285   Curated Info

20

Bartolomé A, Guillén C, Benito M (2010) Role of the TSC1-TSC2 complex in the integration of insulin and glucose signaling involved in pancreatic beta-cell proliferation. Endocrinology 151, 3084-94
20427478   Curated Info

21

Possemato A (2010) CST Curation Set: 9877; Year: 2010; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS*/T*) Immunoaffinity Beads Cat#: 1978
Curated Info

22

Mancini M, et al. (2010) mTOR inhibitor RAD001 (Everolimus) enhances the effects of imatinib in chronic myeloid leukemia by raising the nuclear expression of c-ABL protein. Leuk Res 34, 641-8
19643477   Curated Info

23

Possemato A (2010) CST Curation Set: 9748; Year: 2010; Biosample/Treatment: tissue, liver/AICAR; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS*/T*) Immunoaffinity Beads Cat#: 1978
Curated Info

24

Anastasov N, et al. (2010) C/EBPbeta expression in ALK-positive anaplastic large cell lymphomas is required for cell proliferation and is induced by the STAT3 signaling pathway. Haematologica 95, 760-7
20015877   Curated Info

25

Guo A (2009) CST Curation Set: 7448; Year: 2009; Biosample/Treatment: cell line, 3T3-L1/control; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS*/T*) Immunoaffinity Beads Cat#: 1978
Curated Info

26

Guo A (2009) CST Curation Set: 6160; Year: 2009; Biosample/Treatment: cell line, C2C12/control; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS*/T*) Immunoaffinity Beads Cat#: 1978
Curated Info

27

Guo A (2009) CST Curation Set: 6161; Year: 2009; Biosample/Treatment: cell line, C2C12/control; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS*/T*) Immunoaffinity Beads Cat#: 1978
Curated Info

28

Hoeffer CA, et al. (2008) Removal of FKBP12 enhances mTOR-Raptor interactions, LTP, memory, and perseverative/repetitive behavior. Neuron 60, 832-45
19081378   Curated Info

29

Partovian C, et al. (2008) Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells. Mol Cell 32, 140-9
18851840   Curated Info

30

Possemato A (2008) CST Curation Set: 3853; Year: 2008; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXS/T) (110B7) Rabbit mAb Cat#: 9614, PTMScan(R) Phospho-Akt Substrate Motif (RXXS*/T*) Immunoaffinity Beads Cat#: 1978
Curated Info

31

Russell ST, Eley HL, Wyke SM, Tisdale MJ (2008) Involvement of phosphoinositide 3-kinase and Akt in the induction of muscle protein degradation by proteolysis-inducing factor. Biochem J 409, 751-9
17961125   Curated Info

32

Meske V, Albert F, Ohm TG (2008) Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2A- and glycogen synthase kinase-3 -dependent phosphorylation of Tau. J Biol Chem 283, 100-9
17971449   Curated Info

33

Mukherjee P, et al. (2008) Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain. Mol Cancer 7, 37
18474106   Curated Info

34

Southgate RJ, et al. (2007) FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian skeletal muscle. J Biol Chem 282, 21176-86
17510058   Curated Info

35

Khan N, et al. (2007) Oral consumption of pomegranate fruit extract inhibits growth and progression of primary lung tumors in mice. Cancer Res 67, 3475-82
17389758   Curated Info

36

Du M, Shen QW, Zhu MJ, Ford SP (2007) Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase. J Anim Sci 85, 919-27
17178807   Curated Info

37

d'Abramo C, Ricciarelli R, Pronzato MA, Davies P (2006) Troglitazone, a peroxisome proliferator-activated receptor-gamma agonist, decreases tau phosphorylation in CHOtau4R cells. J Neurochem 98, 1068-77
16787414   Curated Info

38

Cheng SW, Fryer LG, Carling D, Shepherd PR (2004) Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status. J Biol Chem 279, 15719-22
14970221   Curated Info

39

Tirado OM, et al. (2003) The PCPH oncoprotein antagonizes the proapoptotic role of the mammalian target of rapamycin in the response of normal fibroblasts to ionizing radiation. Cancer Res 63, 6290-8
14559816   Curated Info