Thr450
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Home > Phosphorylation Site Page: > Thr450  -  Akt1 (human)

Site Information
tAQMItItPPDQDDs   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447857

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 19 , 20 ) , immunoprecipitation ( 3 , 12 , 15 ) , mass spectrometry ( 2 , 5 , 16 ) , mutation of modification site ( 3 , 9 , 12 , 13 , 14 , 15 , 17 , 19 , 22 ) , peptide sequencing ( 23 ) , phospho-antibody ( 1 , 3 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 , 21 ) , phosphopeptide mapping ( 20 ) , western blotting ( 1 , 3 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 17 , 18 , 19 , 20 , 21 , 23 )
Disease tissue studied:
breast cancer ( 3 , 6 , 8 ) , HER2 positive breast cancer ( 2 ) , luminal A breast cancer ( 2 ) , luminal B breast cancer ( 2 ) , breast cancer, triple negative ( 2 ) , leukemia ( 16 ) , chronic myelogenous leukemia ( 16 ) , liver cancer ( 1 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 12 , 13 , 23 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 19 ) , 3T3 (fibroblast) ( 22 ) , breast ( 2 ) , COS (fibroblast) ( 17 , 19 , 20 ) , epithelial-lens ( 14 ) , HEK293T (epithelial) ( 3 , 9 , 15 ) , HeLa (cervical) ( 6 , 11 ) , HepG2 (hepatic) ( 1 ) , K562 (erythroid) ( 16 ) , L6 (myoblast) ( 23 ) , liver ( 5 ) , MDA-MB-231 (breast cell) ( 3 ) , MDA-MB-435 (breast cell) ( 6 , 8 ) , MEF (fibroblast) ( 15 ) , myocyte-heart ( 18 ) , oocyte ( 10 ) , platelet-blood ( 21 ) , SKBR7 (breast cell) ( 3 ) , SKOV-3 (ovarian) ( 20 )

Upstream Regulation
Regulatory protein:
Akt1 (human) ( 10 ) , MINK (human) ( 3 ) , mTOR (human) ( 10 )
Kinases, in vitro:
mTOR (human) ( 13 )
Putative upstream phosphatases:
PPP1CA (human) ( 14 )
Phosphatases, in vitro:
PPP1CA (human) ( 14 ) , PPP2CA (human) ( 14 )
Treatments:
1-methyladenine ( 10 ) , 2-deoxyglucose ( 6 ) , amino_acid_starvation ( 6 ) , bicyclol ( 1 ) , glucose_starvation ( 6 ) , heat_shock ( 19 ) , insulin ( 12 ) , LY294002 ( 12 ) , okadaic_acid ( 10 , 14 ) , PDGF ( 19 ) , rotenone ( 6 ) , thrombin ( 21 ) , Torin1 ( 8 , 9 ) , TPO ( 21 )

Downstream Regulation
Effects of modification on Akt1:
activity, induced ( 18 ) , enzymatic activity, induced ( 17 , 19 , 22 ) , enzymatic activity, inhibited ( 10 ) , molecular association, regulation ( 15 ) , phosphorylation ( 15 ) , protein conformation ( 15 , 17 ) , protein stabilization ( 15 ) , ubiquitination ( 13 )
Effects of modification on biological processes:
apoptosis, induced ( 18 ) , cell differentiation, altered ( 14 ) , transcription, altered ( 14 ) , translation, altered ( 13 )
Induce interaction with:
PIN1 (human) ( 15 )

References 

1

Wang Y, et al. (2016) Bicyclol induces cell cycle arrest and autophagy in HepG2 human hepatocellular carcinoma cells through the PI3K/AKT and Ras/Raf/MEK/ERK pathways. BMC Cancer 16, 742
27654866   Curated Info

2

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

3

Daulat AM, et al. (2016) PRICKLE1 Contributes to Cancer Cell Dissemination through Its Interaction with mTORC2. Dev Cell 37, 311-25
27184734   Curated Info

4

Lin CH, Liu SY, Lee EH (2016) SUMO modification of Akt regulates global SUMOylation and substrate SUMOylation specificity through Akt phosphorylation of Ubc9 and SUMO1. Oncogene 35, 595-607
25867063   Curated Info

5

Bian Y, et al. (2014) An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics 96, 253-62
24275569   Curated Info

6

Chen CH, et al. (2013) Autoregulation of the mechanistic target of rapamycin (mTOR) complex 2 integrity is controlled by an ATP-dependent mechanism. J Biol Chem 288, 27019-30
23928304   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

Chen CH, Sarbassov dos D (2011) The mTOR (mammalian target of rapamycin) kinase maintains integrity of mTOR complex 2. J Biol Chem 286, 40386-94
21965657   Curated Info

9

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

10

Hiraoka D, Okumura E, Kishimoto T (2011) Turn motif phosphorylation negatively regulates activation loop phosphorylation in Akt. Oncogene 30, 4487-97
21577208   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

Gan X, Wang J, Su B, Wu D (2011) Evidence for direct activation of mTORC2 kinase activity by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 286, 10998-1002
21310961   Curated Info

13

Oh WJ, et al. (2010) mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide. EMBO J 29, 3939-3951
21045808   Curated Info

14

Xiao L, et al. (2010) Protein phosphatase-1 regulates Akt1 signal transduction pathway to control gene expression, cell survival and differentiation. Cell Death Differ 17, 1448-62
20186153   Curated Info

15

Liao Y, et al. (2009) Peptidyl-prolyl cis/trans isomerase Pin1 is critical for the regulation of PKB/Akt stability and activation phosphorylation. Oncogene 28, 2436-45
19448664   Curated Info

16

Stokes M (2008) CST Curation Set: 4390; Year: 2008; Biosample/Treatment: cell line, K562/untreated; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

17

Hauge C, et al. (2007) Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation. EMBO J 26, 2251-61
17446865   Curated Info

18

Shao Z, et al. (2006) c-Jun N-terminal kinases mediate reactivation of Akt and cardiomyocyte survival after hypoxic injury in vitro and in vivo. Circ Res 98, 111-8
16306447   Curated Info

19

Matsuzaki H, Yamamoto T, Kikkawa U (2004) Distinct activation mechanisms of protein kinase B by growth-factor stimulation and heat-shock treatment. Biochemistry 43, 4284-93
15065872   Curated Info

20

Conus NM, et al. (2002) Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase. J Biol Chem 277, 38021-8
12149249   Curated Info

21

Kroner C, Eybrechts K, Akkerman JW (2000) Dual regulation of platelet protein kinase B. J Biol Chem 275, 27790-8
10874027   Curated Info

22

Bellacosa A, et al. (1998) Akt activation by growth factors is a multiple-step process: the role of the PH domain. Oncogene 17, 313-25
9690513   Curated Info

23

Alessi DR, et al. (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15, 6541-51
8978681   Curated Info