Thr444
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Home > Phosphorylation Site Page: > Thr444  -  p70S6K (mouse)

Site Information
RFIGsPRtPVsPVKF   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448358

In vivo Characterization
Methods used to characterize site in vivo:
flow cytometry ( 15 ) , immunoprecipitation ( 12 , 19 ) , mass spectrometry ( 1 , 2 , 3 , 7 , 8 , 9 , 10 , 11 , 13 , 14 , 16 , 20 , 21 , 22 , 25 ) , phospho-antibody ( 4 , 5 , 12 , 15 , 17 , 18 , 19 , 23 , 26 , 27 , 28 , 29 ) , western blotting ( 4 , 5 , 12 , 15 , 17 , 18 , 19 , 23 , 26 , 27 , 28 , 29 )
Disease tissue studied:
lung cancer ( 23 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 3 , 7 ) , 'brain, hippocampus' [FKBP12 (mouse), homozygous knockout] ( 19 ) , 'brain, hippocampus, dentate gyrus' [FKBP12 (mouse), homozygous knockout] ( 19 ) , 293 (epithelial) ( 18 ) , 32D (myeloid) ( 29 ) , 32Dcl3 (myeloid) [FLT3 (mouse), transfection, chimera with human FLT3-ITD mutant (corresponding to wild type P36888 ( 16 ) , 32Dcl3 (myeloid) ( 16 ) , 3T3 (fibroblast) ( 28 ) , BaF3 ('B lymphocyte, precursor') [JAK3 (human), transfection] ( 1 ) , brain ( 9 , 22 ) , C3H10T1/2 (fibroblast) [FGFR2 (mouse), FGFR2 K668E] ( 20 , 21 ) , CHO (fibroblast) [Tau iso8 (human)] ( 26 ) , embryo ( 9 ) , heart ( 18 ) , JB6 CI41 (epidermal) ( 27 ) , liver ( 2 , 9 , 25 ) , lung ( 23 ) , macrophage-bone marrow ( 13 ) , macrophage-bone marrow [DUSP1 (mouse), homozygous knockout] ( 13 ) , macrophage-peritoneum ( 8 ) , MEF (fibroblast) ( 10 , 12 ) , MEF (fibroblast) [DEDD (mouse), homozygous knockout] ( 17 ) , MEF (fibroblast) [TSC2 (mouse), homozygous knockout] ( 10 ) , MN9D ('neuron, mesencephalic') ( 5 ) , mpkCCD (renal) ( 14 ) , myocyte-heart ( 18 ) , pancreas ( 17 ) , stem ( 4 ) , T lymphocyte-lymph node ( 15 ) , T lymphocyte-spleen ( 11 )

Upstream Regulation
Regulatory protein:
DEDD (mouse) ( 17 ) , FKBP12 (mouse) ( 19 ) , mTOR (mouse) ( 24 ) , PKCI (mouse) ( 27 ) , ULK1 (mouse) ( 5 )
Treatments:
adriamycin ( 12 ) , anti-CD3 ( 24 ) , anti-CD3/CD28 ( 24 ) , anti-CTLA-4 ( 15 ) , BAPTA-AM ( 28 ) , benzo(a)pyrene ( 23 ) , BI-D1870 ( 15 ) , calorie_restriction ( 4 ) , catalase ( 27 ) , formate ( 27 ) , H2O2 ( 27 ) , IGF-1 ( 29 ) , IL-2 ( 24 ) , IL-7 ( 24 ) , insulin ( 7 , 28 ) , LPS ( 13 ) , LY294002 ( 7 , 15 , 27 ) , MK-2206 ( 7 ) , NAC ( 27 ) , NADPH ( 27 ) , NP68 ( 15 ) , NTCU ( 23 ) , PD98059 ( 27 ) , pomegranate_wine ( 23 ) , PP2 ( 15 ) , pressure ( 18 ) , rapamycin ( 10 , 12 , 15 , 24 , 27 , 29 ) , SB203580 ( 12 ) , SOD ( 27 ) , Torin1 ( 12 ) , troglitazone ( 26 ) , U0126 ( 15 ) , UV ( 27 ) , wortmannin ( 15 )

Downstream Regulation
Effects of modification on p70S6K:
enzymatic activity, induced ( 29 ) , molecular association, regulation ( 17 )
Effects of modification on biological processes:
cell differentiation, altered ( 29 )
Induce interaction with:
DEDD (mouse) ( 17 )

References 

1

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

2

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

3

Minard AY, et al. (2016) mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes. Cell Rep 17, 29-36
27681418   Curated Info

4

Igarashi M, Guarente L (2016) mTORC1 and SIRT1 Cooperate to Foster Expansion of Gut Adult Stem Cells during Calorie Restriction. Cell 166, 436-50
27345368   Curated Info

5

Li Y, Zhang J, Yang C (2015) UNC-51-like kinase 1 blocks S6k1 phosphorylation contributes to neurodegeneration in Parkinson's disease model in vitro. Biochem Biophys Res Commun 459, 196-200
25680463   Curated Info

6

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

7

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

8

Wu X, et al. (2012) Investigation of receptor interacting protein (RIP3)-dependent protein phosphorylation by quantitative phosphoproteomics. Mol Cell Proteomics 11, 1640-51
22942356   Curated Info

9

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

10

Yu Y, et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322-6
21659605   Curated Info

11

Navarro MN, et al. (2011) Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes. Nat Immunol 12, 352-61
21399638   Curated Info

12

Lai KP, et al. (2010) S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response. EMBO J 29, 2994-3006
20657550   Curated Info

13

Weintz G, et al. (2010) The phosphoproteome of toll-like receptor-activated macrophages. Mol Syst Biol 6, 371
20531401   Curated Info

14

Rinschen MM, et al. (2010) Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor-dependent signaling pathways in renal collecting duct cells. Proc Natl Acad Sci U S A 107, 3882-7
20139300   Curated Info

15

Salmond RJ, Emery J, Okkenhaug K, Zamoyska R (2009) MAPK, phosphatidylinositol 3-kinase, and mammalian target of rapamycin pathways converge at the level of ribosomal protein S6 phosphorylation to control metabolic signaling in CD8 T cells. J Immunol 183, 7388-97
19917692   Curated Info

16

Choudhary C, et al. (2009) Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 36, 326-39
19854140   Curated Info

17

Kurabe N, et al. (2009) The death effector domain-containing DEDD supports S6K1 activity via preventing Cdk1-dependent inhibitory phosphorylation. J Biol Chem 284, 5050-5
19106089   Curated Info

18

Lorenz K, Schmitt JP, Schmitteckert EM, Lohse MJ (2009) A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy. Nat Med 15, 75-83
19060905   Curated Info

19

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

20

Li Y (2008) CST Curation Set: 5592; Year: 2008; Biosample/Treatment: cell line, 10T1/2FGFRK668E/FGF; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: PXpSP, pSPX(K/R) Antibodies Used to Purify Peptides prior to LCMS: Phospho-MAPK/CDK Substrates (PXSP or SPXR/K) (34B2) Rabbit mAb Cat#: 2325, PTMScan(R) Phospho-MAPK/CDK Substrate Motif (PXS*P, S*PXK/R) Immunoaffinity Beads Cat#: 1982
Curated Info

21

Li Y (2008) CST Curation Set: 5590; Year: 2008; Biosample/Treatment: cell line, 10T1/2FGFRK668E/control; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: PXpSP, pSPX(K/R) Antibodies Used to Purify Peptides prior to LCMS: Phospho-MAPK/CDK Substrates (PXSP or SPXR/K) (34B2) Rabbit mAb Cat#: 2325, PTMScan(R) Phospho-MAPK/CDK Substrate Motif (PXS*P, S*PXK/R) Immunoaffinity Beads Cat#: 1982
Curated Info

22

Guo A (2007) CST Curation Set: 2716; Year: 2007; Biosample/Treatment: tissue, brain/-; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: PXpSP, pSPX(K/R) Antibodies Used to Purify Peptides prior to LCMS: Phospho-MAPK/CDK Substrates (PXSP or SPXR/K) (34B2) Rabbit mAb Cat#: 2325, PTMScan(R) Phospho-MAPK/CDK Substrate Motif (PXS*P, S*PXK/R) Immunoaffinity Beads Cat#: 1982
Curated Info

23

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

24

Zheng Y, et al. (2007) A role for mammalian target of rapamycin in regulating T cell activation versus anergy. J Immunol 178, 2163-70
17277121   Curated Info

25

Villén J, Beausoleil SA, Gerber SA, Gygi SP (2007) Large-scale phosphorylation analysis of mouse liver. Proc Natl Acad Sci U S A 104, 1488-93
17242355   Curated Info

26

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

27

Huang C, et al. (2002) Ultraviolet-induced phosphorylation of p70(S6K) at Thr(389) and Thr(421)/Ser(424) involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C. Cancer Res 62, 5689-97
12384526   Curated Info

28

Worrall DS, Olefsky JM (2002) The effects of intracellular calcium depletion on insulin signaling in 3T3-L1 adipocytes. Mol Endocrinol 16, 378-89
11818508   Curated Info

29

Valentinis B, et al. (2000) Insulin receptor substrate-1, p70S6K, and cell size in transformation and differentiation of hemopoietic cells. J Biol Chem 275, 25451-9
10846175   Curated Info