Thr24
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Home > Phosphorylation Site Page: > Thr24  -  FOXO1A (mouse)

Site Information
LPRQRSCtWPLPRPE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448560
Associated spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 24 , 25 ) , immunoassay ( 8 ) , immunoprecipitation ( 2 , 9 ) , mass spectrometry ( 3 , 5 , 17 , 18 , 19 ) , mutation of modification site ( 2 , 6 , 23 , 24 , 25 , 26 ) , phospho-antibody ( 1 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 20 , 21 , 22 , 23 ) , phosphopeptide mapping ( 5 , 25 ) , western blotting ( 1 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 20 , 21 , 22 , 26 )
Disease tissue studied:
leukemia ( 4 ) , T cell leukemia ( 4 ) , liver cancer ( 6 ) , diabetes mellitus ( 21 ) , type 2 diabetes ( 21 )
Relevant cell line - cell type - tissue:
'brain, embryonic' ( 17 , 18 ) , 'muscle, skeletal' [RICTOR (mouse), homozygous knockout] ( 16 ) , 3T3-L1 (fibroblast) ( 21 ) , B lymphocyte-spleen ( 8 ) , brain ( 19 ) , C2C12 (myoblast) ( 9 ) , CV1 (fibroblast) ( 25 ) , E.coli (bacterial) ( 2 ) , Fao (hepatic) ( 6 ) , HEK293T (epithelial) ( 4 ) , hepatocyte ( 24 ) , hepatocyte-liver ( 5 ) , hepatocyte-liver [TSC1 (mouse), homozygous knockout] ( 10 ) , Jurkat E6-1 (T lymphocyte) ( 4 ) , liver ( 1 , 5 , 13 ) , lymphocyte ( 3 ) , MEF (fibroblast) ( 7 , 11 , 15 , 20 ) , MEF (fibroblast) [Sin1 (mouse), homozygous knockout] ( 14 ) , muscle ( 21 ) , myoblast ( 22 ) , SV40 ( 23 , 26 )

Upstream Regulation
Regulatory protein:
INSR (mouse) ( 24 ) , PTEN (mouse) ( 15 ) , RICTOR (mouse) ( 15 , 16 ) , Sin1 (mouse) ( 20 ) , TSC1 (mouse) ( 10 )
Putative in vivo kinases:
Akt1 (mouse) ( 23 )
Kinases, in vitro:
Akt1 (mouse) ( 25 )
Treatments:
anti-IgM ( 8 ) , Dynasore ( 8 ) , fasting ( 13 ) , IGF-1 ( 23 , 24 ) , insulin ( 1 , 10 , 16 , 20 , 23 , 24 , 26 ) , KU-0063794 ( 3 ) , rapamycin ( 7 , 10 , 22 ) , refeeding ( 13 ) , rosiglitazone ( 21 ) , serum ( 20 ) , wortmannin ( 25 )

Downstream Regulation
Effects of modification on FOXO1A:
intracellular localization ( 24 , 25 )
Effects of modification on biological processes:
transcription, inhibited ( 6 , 24 )

Disease / Diagnostics Relevance
Relevant diseases:
type 2 diabetes ( 21 )

References 

1

Batista TM, et al. (2020) Arrestin domain-containing 3 (Arrdc3) modulates insulin action and glucose metabolism in liver. Proc Natl Acad Sci U S A 117, 6733-6740
32156724   Curated Info

2

Yalley A, et al. (2016) Loss of Interdependent Binding by the FoxO1 and FoxA1/A2 Forkhead Transcription Factors Culminates in Perturbation of Active Chromatin Marks and Binding of Transcriptional Regulators at Insulin-sensitive Genes. J Biol Chem 291, 8848-61
26929406   Curated Info

3

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

4

Du X, et al. (2014) Mst1/Mst2 Regulate Development and Function of Regulatory T Cells through Modulation of Foxo1/Foxo3 Stability in Autoimmune Disease. J Immunol 192, 1525-35
24453252   Curated Info

5

Ozcan L, et al. (2012) Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity. Cell Metab 15, 739-51
22503562   Curated Info

6

Jiao P, Feng B, Xu H (2012) Mapping MKP-3/FOXO1 Interaction and Evaluating the Effect on Gluconeogenesis. PLoS One 7, e41168
22848439   Curated Info

7

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

8

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

9

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

10

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

11

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

12

Rodgers JT, Vogel RO, Puigserver P (2011) Clk2 and B56β Mediate Insulin-Regulated Assembly of the PP2A Phosphatase Holoenzyme Complex on Akt. Mol Cell 41, 471-9
21329884   Curated Info

13

Rodgers JT, Haas W, Gygi SP, Puigserver P (2010) Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis. Cell Metab 11, 23-34
20074525   Curated Info

14

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

15

Guertin DA, et al. (2009) mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice. Cancer Cell 15, 148-59
19185849   Curated Info

16

Kumar A, et al. (2008) Muscle-specific deletion of rictor impairs insulin-stimulated glucose transport and enhances Basal glycogen synthase activity. Mol Cell Biol 28, 61-70
17967879   Curated Info

17

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

18

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

19

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

20

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

21

Wang X, et al. (2006) Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology 147, 4160-8
16777975   Curated Info

22

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

23

Nakae J, et al. (2001) Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt. Biochemistry 40, 11768-76
11570877   Curated Info

24

Nakae J, Barr V, Accili D (2000) Differential regulation of gene expression by insulin and IGF-1 receptors correlates with phosphorylation of a single amino acid residue in the forkhead transcription factor FKHR. EMBO J 19, 989-96
10698940   Curated Info

25

Biggs WH, et al. (1999) Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci U S A 96, 7421-6
10377430   Curated Info

26

Nakae J, Park BC, Accili D (1999) Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway. J Biol Chem 274, 15982-5
10347145   Curated Info