Thr32
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Home > Phosphorylation Site Page: > Thr32  -  FOXO3A (mouse)

Site Information
QSRPRSCtWPLQRPE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448602
Associated spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
electrophoretic mobility shift ( 37 , 43 ) , immunoassay ( 6 ) , immunoprecipitation ( 8 , 19 ) , mass spectrometry ( 1 , 12 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ) , mutation of modification site ( 38 , 41 , 43 , 44 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 8 , 9 , 10 , 13 , 14 , 15 , 16 , 18 , 19 , 21 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 8 , 9 , 10 , 13 , 14 , 15 , 16 , 18 , 19 , 21 , 30 , 31 , 32 , 33 , 37 , 39 , 40 , 41 , 43 , 44 )
Disease tissue studied:
leukemia ( 4 ) , chronic myelogenous leukemia ( 4 ) , neuroblastoma ( 37 )
Relevant cell line - cell type - tissue:
'brain, embryonic' ( 23 , 24 ) , 'fat, brown'-'fat, brown' ( 13 ) , 'muscle, skeletal' ( 2 , 13 ) , 'neuron, cerebellar granule'-brain ( 44 ) , 'stem, neural' ( 16 ) , 293 (epithelial) ( 14 , 43 ) , 3T3 (fibroblast) [INSR (mouse), transfection] ( 19 ) , 3T3 (fibroblast) ( 19 , 33 ) , B lymphocyte-spleen ( 6 ) , BaF3 ('B lymphocyte, precursor') ( 19 , 21 , 38 ) , brain ( 25 , 26 ) , BV-173 (myeloid) ( 35 ) , C2C12 (myoblast) ( 8 ) , C2C12-D (muscle cell) ( 27 , 28 ) , COS (fibroblast) ( 19 , 38 ) , CTLL-2 (T lymphocyte) ( 40 ) , Dede (fibroblast) ( 41 , 43 , 44 ) , DLD1 (intestinal) ( 34 ) , erythroid ( 42 ) , GD25 (fibroblast) ( 39 ) , HCD 57 (erythroid) ( 42 ) , HCT116 (intestinal) ( 34 ) , HEK293T (epithelial) ( 43 , 44 ) , hepatocyte-liver [TSC1 (mouse), homozygous knockout] ( 9 ) , K562 (erythroid) ( 4 ) , kidney ( 12 ) , liver ( 13 , 22 ) , lymphocyte ( 1 ) , M1 (myeloid) ( 4 ) , MEF (fibroblast) ( 3 , 5 , 10 , 14 , 30 , 31 , 32 ) , MEF (fibroblast) [IGF1R (mouse)] ( 36 ) , MEF (fibroblast) [Sin1 (mouse), homozygous knockout] ( 18 ) , MMC (mesangial) ( 29 ) , myocyte-heart ( 15 ) , SH-SY5Y (neural crest) ( 37 ) , spleen ( 12 )

Upstream Regulation
Regulatory protein:
FGFR1 (human) ( 21 ) , FLT3 (human) ( 38 ) , GILZ (human) ( 4 ) , ITGB1 (human) ( 39 ) , LST8 (mouse) ( 30 ) , RICTOR (mouse) ( 13 , 14 , 30 ) , SHC1 (mouse) ( 29 ) , Sin1 (mouse) ( 32 ) , SIRT1 (mouse) ( 11 ) , TMEM55B (mouse) ( 17 ) , TSC1 (mouse) ( 31 ) , TSC2 (mouse) ( 31 )
Putative in vivo kinases:
Akt1 (human) ( 15 , 43 , 44 ) , SGK1 (human) ( 43 )
Kinases, in vitro:
Akt1 (mouse) ( 44 )
Treatments:
angiotensin_2 ( 11 ) , anti-IgM ( 6 ) , BDNF ( 37 ) , calyculin_A ( 37 ) , ciclosporin ( 37 ) , colforsin ( 36 ) , differentiation ( 16 ) , Dynasore ( 6 ) , EGF ( 17 ) , Epo ( 42 ) , ethanol ( 15 ) , exercise ( 2 ) , fasting ( 11 ) , FK506 ( 37 ) , FL ( 38 ) , glucose ( 29 ) , H2O2 ( 33 ) , IBMX ( 36 ) , IGF-1 ( 31 , 41 , 43 , 44 ) , IL-2 ( 40 ) , IL-3 ( 19 ) , imatinib ( 35 ) , insulin ( 9 , 11 , 13 , 30 , 32 ) , KU-0063794 ( 1 ) , LY294002 ( 37 , 40 , 42 , 44 ) , NBD_peptide ( 3 ) , okadaic_acid ( 37 ) , PD98059 ( 37 ) , PDGF ( 31 ) , rapamycin ( 5 , 9 , 19 , 31 ) , SCF ( 42 ) , serum ( 14 , 31 , 32 , 33 ) , starvation_medium ( 3 ) , thapsigargin ( 37 ) , U0126 ( 21 , 33 , 36 ) , wortmannin ( 21 , 31 , 33 )

Downstream Regulation
Effects of modification on FOXO3A:
intracellular localization ( 4 , 29 , 38 , 41 , 43 , 44 ) , molecular association, regulation ( 41 , 42 , 44 ) , protein degradation ( 4 )
Effects of modification on biological processes:
apoptosis, altered ( 17 ) , apoptosis, inhibited ( 4 , 43 ) , cell cycle regulation ( 43 ) , cell growth, altered ( 17 ) , cytoskeletal reorganization ( 17 ) , signaling pathway regulation ( 13 ) , transcription, inhibited ( 4 , 43 ) , translation, inhibited ( 4 )
Induce interaction with:
14-3-3 beta (human) ( 41 ) , 14-3-3 zeta (mouse) ( 44 )
Inhibit interaction with:
p300 (human) ( 42 )

References 

1

Hukelmann JL, et al. (2016) The cytotoxic T cell proteome and its shaping by the kinase mTOR. Nat Immunol 17, 104-12
26551880   Curated Info

2

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

3

Comb WC, et al. (2012) p85α SH2 Domain Phosphorylation by IKK Promotes Feedback Inhibition of PI3K and Akt in Response to Cellular Starvation. Mol Cell 45, 719-30
22342344   Curated Info

4

Joha S, et al. (2012) GILZ inhibits the mTORC2/AKT pathway in BCR-ABL(+) cells. Oncogene 31, 1419-30
21804606   Curated Info

5

Warfel NA, Niederst M, Newton AC (2011) Disruption of the interface between the pleckstrin homology (PH) and kinase domains of Akt protein is sufficient for hydrophobic motif site phosphorylation in the absence of mTORC2. J Biol Chem 286, 39122-9
21908613   Curated Info

6

Chaturvedi A, et al. (2011) Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments. Nat Immunol 12, 1119-26
21964606   Curated Info

7

Guo JP, Coppola D, Cheng JQ (2011) IKBKE protein activates Akt independent of phosphatidylinositol 3-kinase/PDK1/mTORC2 and the pleckstrin homology domain to sustain malignant transformation. J Biol Chem 286, 37389-98
21908616   Curated Info

8

Zhang G, Jin B, Li YP (2011) C/EBPβ mediates tumour-induced ubiquitin ligase atrogin1/MAFbx upregulation and muscle wasting. EMBO J 30, 4323-35
21847090   Curated Info

9

Yecies JL, et al. (2011) Akt Stimulates Hepatic SREBP1c and Lipogenesis through Parallel mTORC1-Dependent and Independent Pathways. Cell Metab 14, 21-32
21723501   Curated Info

10

Xie X, et al. (2011) IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation. Proc Natl Acad Sci U S A 108, 6474-9
21464307   Curated Info

11

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

12

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

13

Kumar A, et al. (2010) Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolism. Diabetes 59, 1397-406
20332342   Curated Info

14

Treins C, et al. (2010) Rictor is a novel target of p70 S6 kinase-1. Oncogene 29, 1003-16
19935711   Curated Info

15

Ma H, Li J, Gao F, Ren J (2009) Aldehyde dehydrogenase 2 ameliorates acute cardiac toxicity of ethanol: role of protein phosphatase and forkhead transcription factor. J Am Coll Cardiol 54, 2187-96
19942091   Curated Info

16

Renault VM, et al. (2009) FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell 5, 527-39
19896443   Curated Info

17

Ivetac I, et al. (2009) Regulation of PI(3)K/Akt signalling and cellular transformation by inositol polyphosphate 4-phosphatase-1. EMBO Rep 10, 487-93
19325558   Curated Info

18

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

19

van Gorp AG, et al. (2009) AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B. Oncogene 28, 95-106
18836482   Curated Info

20

Surucu B, et al. (2008) In vivo analysis of protein kinase B (PKB)/Akt regulation in DNA-PKcs-null mice reveals a role for PKB/Akt in DNA damage response and tumorigenesis. J Biol Chem 283, 30025-33
18757368   Curated Info

21

Dong S, et al. (2007) 14-3-3 Integrates prosurvival signals mediated by the AKT and MAPK pathways in ZNF198-FGFR1-transformed hematopoietic cells. Blood 110, 360-9
17389761   Curated Info

22

Guo A (2007) CST Curation Set: 3017; Year: 2007; Biosample/Treatment: tissue, liver/-; 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 (RXRXXT-P) (81E12B5) Rabbit mAb Cat#: 10003
Curated Info

23

Guo A (2007) CST Curation Set: 3022; Year: 2007; Biosample/Treatment: tissue, brain, embryonic/-; 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 (RXRXXT-P) (81E12B5) Rabbit mAb Cat#: 10003
Curated Info

24

Guo A (2007) CST Curation Set: 3024; Year: 2007; Biosample/Treatment: tissue, brain, embryonic/-; 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 (RXRXXT-P) (81E12B5) Rabbit mAb Cat#: 10003
Curated Info

25

Guo A (2007) CST Curation Set: 3025; Year: 2007; Biosample/Treatment: tissue, brain/-; 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 (RXRXXT-P) (81E12B5) Rabbit mAb Cat#: 10003
Curated Info

26

Guo A (2007) CST Curation Set: 3026; Year: 2007; Biosample/Treatment: tissue, brain/-; 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 (RXRXXT-P) (81E12B5) Rabbit mAb Cat#: 10003
Curated Info

27

Guo A (2007) CST Curation Set: 2750; Year: 2007; Biosample/Treatment: cell line, C2C12-D/Insulin; 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 (RXRXXT-P) (81E12B5) Rabbit mAb Cat#: 10003
Curated Info

28

Guo A (2007) CST Curation Set: 2751; Year: 2007; Biosample/Treatment: cell line, C2C12-D/-; 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 (RXRXXT-P) (81E12B5) Rabbit mAb Cat#: 10003
Curated Info

29

Chintapalli J, et al. (2007) Inhibition of wild-type p66ShcA in mesangial cells prevents glycooxidant-dependent FOXO3a regulation and promotes the survival phenotype. Am J Physiol Renal Physiol 292, F523-30
17077388   Curated Info

30

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

31

Zhang HH, et al. (2006) S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol Cell 24, 185-97
17052453   Curated Info

32

Jacinto E, et al. (2006) SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 127, 125-37
16962653   Curated Info

33

Hu Y, et al. (2005) ERK phosphorylates p66shcA on Ser36 and subsequently regulates p27kip1 expression via the Akt-FOXO3a pathway: implication of p27kip1 in cell response to oxidative stress. Mol Biol Cell 16, 3705-18
15930121   Curated Info

34

Samuels Y, et al. (2005) Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7, 561-73
15950905   Curated Info

35

Essafi A, et al. (2005) Direct transcriptional regulation of Bim by FoxO3a mediates STI571-induced apoptosis in Bcr-Abl-expressing cells. Oncogene 24, 2317-29
15688014   Curated Info

36

Kuiperij HB, et al. (2005) Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP. Oncogene 24, 2087-95
15688004   Curated Info

37

Zhu W, Bijur GN, Styles NA, Li X (2004) Regulation of FOXO3a by brain-derived neurotrophic factor in differentiated human SH-SY5Y neuroblastoma cells. Brain Res Mol Brain Res 126, 45-56
15207915   Curated Info

38

Scheijen B, Ngo HT, Kang H, Griffin JD (2004) FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins. Oncogene 23, 3338-49
14981546   Curated Info

39

Pankov R, et al. (2003) Specific beta1 integrin site selectively regulates Akt/protein kinase B signaling via local activation of protein phosphatase 2A. J Biol Chem 278, 18671-81
12637511   Curated Info

40

Stahl M, et al. (2002) The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol 168, 5024-31
11994454   Curated Info

41

Brunet A, et al. (2002) 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. J Cell Biol 156, 817-28
11864996   Curated Info

42

Mahmud DL, et al. (2002) Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells. Oncogene 21, 1556-62
11896584   Curated Info

43

Brunet A, et al. (2001) Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol Cell Biol 21, 952-65
11154281   Curated Info

44

Brunet A, et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857-68
10102273   Curated Info