Ser64
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Home > Phosphorylation Site Page: > Ser64  -  4E-BP1 (mouse)

Site Information
FLMECRNsPVAKtPP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447527

In vivo Characterization
Methods used to characterize site in vivo:
electrophoretic mobility shift ( 35 ) , immunoprecipitation ( 8 , 20 ) , mass spectrometry ( 2 , 4 , 5 , 6 , 7 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 21 , 22 , 25 , 26 , 28 ) , phospho-antibody ( 3 , 8 , 19 , 20 , 23 , 24 , 27 , 30 , 31 , 32 , 33 , 34 , 35 ) , western blotting ( 3 , 8 , 10 , 19 , 20 , 23 , 24 , 27 , 30 , 31 , 32 , 33 , 34 )
Disease tissue studied:
lung cancer ( 30 ) , lymphoma ( 23 ) , T cell lymphoma ( 23 ) , melanoma skin cancer ( 28 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 5 , 7 , 15 ) , 'fat, brown' ( 22 ) , 'muscle, skeletal' ( 33 ) , 32Dcl3 (myeloid) [FLT3 (mouse), transfection, chimera with human FLT3-ITD mutant (corresponding to wild type P36888 ( 26 ) , 32Dcl3 (myeloid) ( 26 ) , 3T3 (fibroblast) [KRas (human), transfection] ( 13 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 35 ) , 3T3 (fibroblast) ( 13 , 20 ) , BaF3 ('B lymphocyte, precursor') [JAK3 (human), transfection] ( 2 ) , beta-pancreas [INSR (mouse), transgenic] ( 24 ) , brain ( 22 ) , C2C12 (myoblast) ( 18 ) , heart ( 16 , 22 ) , HEK293T (epithelial) ( 19 , 20 ) , hepatocyte-liver ( 3 ) , HL-1 (myocyte) ( 11 ) , JB (epithelial) ( 34 ) , kidney ( 22 ) , liver ( 3 , 4 , 14 , 17 , 22 ) , liver [leptin (mouse), homozygous knockout] ( 17 ) , liver [LKB1 (mouse), homozygous knockout] ( 32 ) , lung ( 22 , 30 ) , macrophage-bone marrow ( 25 ) , macrophage-bone marrow [DUSP1 (mouse), homozygous knockout] ( 25 ) , MC3T3-E1 (preosteoblast) ( 6 ) , MEF (fibroblast) ( 19 , 31 ) , MEF (fibroblast) [Sin1 (mouse), homozygous knockout] ( 27 ) , MEF (fibroblast) [TSC2 (mouse), homozygous knockout] ( 21 ) , muscle [LKB1 (mouse), homozygous knockout] ( 32 ) , NMuMG (epithelial) ( 8 ) , oocyte ( 10 ) , ovary ( 10 ) , pancreas ( 22 ) , RAW 264.7 (macrophage) ( 9 ) , skin [mGluR1 (mouse), transgenic, TG mutant mice] ( 28 ) , spleen ( 22 ) , stromal ( 12 ) , testis ( 22 ) , WEHI-7 (T lymphocyte) ( 23 )

Upstream Regulation
Regulatory protein:
AMPKA1 (mouse) ( 19 ) , CAMK2G (mouse) ( 3 ) , Fyn (mouse) ( 23 ) , LKB1 (mouse) ( 32 ) , LST8 (mouse) ( 31 ) , RHEB (mouse) ( 19 ) , RRAGC (mouse) ( 19 ) , Sin1 (mouse) ( 27 )
Putative in vivo kinases:
MSK1 (human) ( 34 ) , mTOR (mouse) ( 35 ) , P38A (human) ( 34 )
Kinases, in vitro:
MSK1 (human) ( 34 )
Treatments:
acadesine ( 19 ) , amino_acids ( 19 , 33 ) , benzo(a)pyrene ( 30 ) , BX795 ( 27 ) , DEN ( 3 ) , dexamethasone ( 23 ) , glucose ( 24 ) , H-89 ( 34 ) , IBMX ( 19 ) , IGF-1 ( 33 ) , INK-128 ( 8 ) , insulin ( 8 , 15 , 19 , 24 , 27 , 35 ) , ischemia ( 12 ) , LY294002 ( 15 ) , meal feeding ( 32 , 33 ) , NKH_477 ( 19 ) , NTCU ( 30 ) , PD169316 ( 34 ) , PD98059 ( 34 ) , PIK90 ( 27 ) , pomegranate_wine ( 30 ) , PP242 ( 27 ) , PTH(1-34) ( 6 ) , rapamycin ( 20 , 21 , 27 , 33 , 34 , 35 ) , SB202190 ( 34 ) , serum_starvation ( 19 ) , Torin1 ( 8 , 20 ) , U0126 ( 24 , 34 ) , UV ( 34 ) , wortmannin ( 24 , 34 ) , XL-147 ( 1 )

References 

1

Bosbach B, et al. (2017) Direct engagement of the PI3K pathway by mutant KIT dominates oncogenic signaling in gastrointestinal stromal tumor. Proc Natl Acad Sci U S A 114, E8448-E8457
28923937   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

Meng Z, et al. (2017) CAMK2γ antagonizes mTORC1 activation during hepatocarcinogenesis. Oncogene 36, 2446-2456
27819676   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

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

6

Williams GR, et al. (2016) Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics. Methods 92, 36-50
26160508   Curated Info

7

Parker BL, et al. (2015) Targeted phosphoproteomics of insulin signaling using data-independent acquisition mass spectrometry. Sci Signal 8, rs6
26060331   Curated Info

8

Im YK, et al. (2015) The ShcA adaptor activates AKT signaling to potentiate breast tumor angiogenesis by stimulating VEGF mRNA translation in a 4E-BP-dependent manner. Oncogene 34, 1729-35
24837366   Curated Info

9

Pinto SM, et al. (2015) Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics 15, 532-44
25367039   Curated Info

10

Zhang H, et al. (2014) Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice. Curr Biol 24, 2501-8
25438940   Curated Info

11

Reinartz M, Raupach A, Kaisers W, Gödecke A (2014) AKT1 and AKT2 induce distinct phosphorylation patterns in HL-1 cardiac myocytes. J Proteome Res 13, 4232-45
25162660   Curated Info

12

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

13

Gnad F, et al. (2013) Systems-wide Analysis of K-Ras, Cdc42, and PAK4 Signaling by Quantitative Phosphoproteomics. Mol Cell Proteomics 12, 2070-80
23608596   Curated Info

14

Wilson-Grady JT, Haas W, Gygi SP (2013) Quantitative comparison of the fasted and re-fed mouse liver phosphoproteomes using lower pH reductive dimethylation. Methods 61, 277-86
23567750   Curated Info

15

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

16

Lundby A, et al. (2013) In vivo phosphoproteomics analysis reveals the cardiac targets of β-adrenergic receptor signaling. Sci Signal 6, rs11
23737553   Curated Info

17

Grimsrud PA, et al. (2012) A quantitative map of the liver mitochondrial phosphoproteome reveals posttranslational control of ketogenesis. Cell Metab 16, 672-83
23140645   Curated Info

18

Knight JD, et al. (2012) A novel whole-cell lysate kinase assay identifies substrates of the p38 MAPK in differentiating myoblasts. Skelet Muscle 2, 5
22394512   Curated Info

19

Xie J, et al. (2011) cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity. Cell Signal 23, 1927-35
21763421   Curated Info

20

Peterson TR, et al. (2011) mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell 146, 408-20
21816276   Curated Info

21

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

22

Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89
21183079   Curated Info

23

Harr MW, et al. (2010) Glucocorticoids downregulate Fyn and inhibit IP(3)-mediated calcium signaling to promote autophagy in T lymphocytes. Autophagy 6, 912-21
20814235   Curated Info

24

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

25

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

26

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

27

Feldman ME, et al. (2009) Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 7, e38
19209957   Curated Info

28

Zanivan S, et al. (2008) Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry. J Proteome Res 7, 5314-26
19367708   Curated Info

29

Gwinn DM, et al. (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30, 214-26
18439900   Curated Info

30

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

31

Guertin DA, et al. (2006) Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 11, 859-71
17141160   Curated Info

32

Shaw RJ, et al. (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310, 1642-6
16308421   Curated Info

33

Ohanna M, et al. (2005) Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat Cell Biol 7, 286-94
15723049   Curated Info

34

Liu G, et al. (2002) Phosphorylation of 4E-BP1 is mediated by the p38/MSK1 pathway in response to UVB irradiation. J Biol Chem 277, 8810-6
11777913   Curated Info

35

Mothe-Satney I, et al. (2000) Mammalian target of rapamycin-dependent phosphorylation of PHAS-I in four (S/T)P sites detected by phospho-specific antibodies. J Biol Chem 275, 33836-43
10942774   Curated Info