Ser447
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Home > Phosphorylation Site Page: > Ser447  -  p70S6K (rat)

Site Information
GsPRtPVsPVKFsPG   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448357
Associated spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 18 , 23 , 26 ) , mass spectrometry ( 2 , 3 , 9 ) , mutation of modification site ( 7 , 25 ) , peptide sequencing ( 26 ) , phospho-antibody ( 1 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 ) , phosphoamino acid analysis ( 26 ) , phosphopeptide mapping ( 26 ) , western blotting ( 1 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 25 )
Disease tissue studied:
breast cancer ( 6 ) , HNSCC ( 1 ) , liver cancer ( 6 )
Relevant cell line - cell type - tissue:
'brain, hippocampus' ( 11 ) , 'brain, striatum' ( 11 ) , 'muscle, skeletal' ( 13 , 17 , 20 ) , 'muscle, smooth'-thoracic aorta ( 19 ) , 'neuron, cortical'-brain ( 5 ) , 'neuron, hippocampal'-brain ( 5 ) , 293 (epithelial) ( 25 ) , adipocyte-adipose tissue ( 23 ) , adipose tissue ( 2 ) , brain ( 9 ) , Cal27 (squamous) ( 1 ) , CHO (fibroblast) [EphB1 (human), transfection] ( 25 ) , COS (fibroblast) ( 7 ) , H4IIe (hepatic) ( 18 ) , H9c2 (myoblast) ( 10 ) , HEK293T (epithelial) ( 7 ) , hepatic stellate ( 15 ) , L6E9 ( 24 ) , liver ( 3 , 6 , 16 ) , mammary gland ( 6 ) , myocardium ( 12 ) , myocyte-heart ( 8 , 21 ) , neuron-'brain, cerebral cortex' ( 7 ) , sertoli-testis ( 14 ) , stomach ( 2 ) , Swiss 3T3 (fibroblast) ( 26 ) , UMUC6 (bladder cell) ( 1 )

Upstream Regulation
Regulatory protein:
CAB39 (human) ( 8 ) , CDK5 (rat) ( 7 ) , LKB1 (mouse) ( 8 ) , STRAD (human) ( 8 )
Kinases, in vitro:
CDK1 (human) ( 26 ) , CDK5 (human) ( 7 ) , ERK2 (human) ( 26 )
Treatments:
adrenalectomy ( 12 ) , amino_acids ( 16 , 17 ) , BAPTA-AM ( 5 ) , BDNF ( 5 ) , C2-ceramide ( 23 ) , calyculin_A ( 18 ) , colforsin ( 14 ) , CPCCOEt ( 11 ) , depolarization ( 5 ) , development ( 13 ) , DHC ( 23 ) , DHPG ( 11 ) , EGTA ( 5 ) , ethanol ( 17 , 20 ) , food deprivation ( 6 ) , GW_8510 ( 7 ) , H2O2 ( 21 ) , IGF-1 ( 20 , 24 ) , IgG ( 5 ) , insulin ( 7 , 10 , 12 , 14 , 18 , 20 , 23 , 24 , 25 ) , K252a ( 5 ) , KN-62 ( 5 ) , KN-93 ( 5 ) , lapatinib ( 1 ) , LY294002 ( 1 , 5 , 14 , 15 , 24 ) , mechanical stress ( 13 ) , metoprolol ( 12 ) , MPEP ( 11 ) , NMDA ( 5 ) , osmotic_stress ( 18 ) , PD98059 ( 11 ) , PDGF ( 15 , 24 ) , rapamycin ( 5 , 7 , 10 , 14 , 15 , 16 , 21 , 25 ) , resveratrol ( 19 ) , serum ( 19 , 25 ) , TGF-beta ( 15 ) , TNF ( 15 ) , U0126 ( 5 ) , U73122 ( 5 ) , urofollitropin ( 14 ) , vanadate ( 18 ) , W-13 ( 5 ) , wortmannin ( 18 , 21 , 24 , 25 ) , XeC ( 5 )

Downstream Regulation
Effects of modification on p70S6K:
enzymatic activity, induced ( 14 , 22 )

References 

1

Axelrod MJ, et al. (2014) p70S6 kinase is a critical node that integrates HER-family and PI3 kinase signaling networks. Cell Signal 26, 1627-35
24662264   Curated Info

2

Lundby A, et al. (2012) Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun 3, 876
22673903   Curated Info

3

Demirkan G, et al. (2011) Phosphoproteomic Profiling of In Vivo Signaling in Liver by the Mammalian Target of Rapamycin Complex 1 (mTORC1). PLoS One 6, e21729
21738781   Curated Info

4

Blancquaert S, et al. (2010) cAMP-dependent activation of mammalian target of rapamycin (mTOR) in thyroid cells. Implication in mitogenesis and activation of CDK4. Mol Endocrinol 24, 1453-68
20484410   Curated Info

5

Zhou X, et al. (2010) Intracellular calcium and calmodulin link brain-derived neurotrophic factor to p70S6 kinase phosphorylation and dendritic protein synthesis. J Neurosci Res 88, 1420-32
20029971   Curated Info

6

Jiang W, Zhu Z, Thompson HJ (2008) Dietary energy restriction modulates the activity of AMP-activated protein kinase, Akt, and mammalian target of rapamycin in mammary carcinomas, mammary gland, and liver. Cancer Res 68, 5492-9
18593953   Curated Info

7

Hou Z, He L, Qi RZ (2007) Regulation of s6 kinase 1 activation by phosphorylation at ser-411. J Biol Chem 282, 6922-8
17220300   Curated Info

8

Noga AA, et al. (2007) Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy. Am J Physiol Heart Circ Physiol 292, H1460-9
17098823   Curated Info

9

Guo A (2007) CST Curation Set: 2243; Year: 2007; Biosample/Treatment: tissue, brain/ischemia 20'; 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

10

Nascimento EB, et al. (2006) Insulin-mediated phosphorylation of the proline-rich Akt substrate PRAS40 is impaired in insulin target tissues of high-fat diet-fed rats. Diabetes 55, 3221-8
17130464   Curated Info

11

Page G, et al. (2006) Group I metabotropic glutamate receptors activate the p70S6 kinase via both mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK 1/2) signaling pathways in rat striatal and hippocampal synaptoneurosomes. Neurochem Int 49, 413-21
16549223   Curated Info

12

Samuelsson AM, et al. (2006) Hyperinsulinemia: effect on cardiac mass/function, angiotensin II receptor expression, and insulin signaling pathways. Am J Physiol Heart Circ Physiol 291, H787-96
16565309   Curated Info

13

Thomson DM, Gordon SE (2006) Impaired overload-induced muscle growth is associated with diminished translational signalling in aged rat fast-twitch skeletal muscle. J Physiol 574, 291-305
16627569   Curated Info

14

Lécureuil C, et al. (2005) Follicle-stimulating hormone activates p70 ribosomal protein S6 kinase by protein kinase A-mediated dephosphorylation of Thr 421/Ser 424 in primary Sertoli cells. Mol Endocrinol 19, 1812-20
15774499   Curated Info

15

Gäbele E, et al. (2005) The role of p70S6K in hepatic stellate cell collagen gene expression and cell proliferation. J Biol Chem 280, 13374-82
15677443   Curated Info

16

Schliess F, et al. (2004) Involvement of integrins and Src in insulin signaling toward autophagic proteolysis in rat liver. J Biol Chem 279, 21294-301
14985360   Curated Info

17

Lang CH, et al. (2003) Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G, and mTOR in skeletal muscle. Am J Physiol Endocrinol Metab 285, E1205-15
12944322   Curated Info

18

Lornejad-Schäfer MR, et al. (2003) Osmotic regulation of insulin-induced mitogen-activated protein kinase phosphatase (MKP-1) expression in H4IIE rat hepatoma cells. Biochem J 371, 609-19
12529177   Curated Info

19

Haider UG, et al. (2003) Resveratrol increases serine15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Mol Pharmacol 63, 925-32
12644594   Curated Info

20

Kumar V, Frost RA, Lang CH (2002) Alcohol impairs insulin and IGF-I stimulation of S6K1 but not 4E-BP1 in skeletal muscle. Am J Physiol Endocrinol Metab 283, E917-28
12376318   Curated Info

21

Tu VC, Bahl JJ, Chen QM (2002) Signals of oxidant-induced cardiomyocyte hypertrophy: key activation of p70 S6 kinase-1 and phosphoinositide 3-kinase. J Pharmacol Exp Ther 300, 1101-10
11861821   Curated Info

22

Shah OJ, et al. (2002) The activated glucocorticoid receptor modulates presumptive autoregulation of ribosomal protein S6 protein kinase, p70 S6K. J Biol Chem 277, 2525-33
11705993   Curated Info

23

Teruel T, Hernandez R, Lorenzo M (2001) Ceramide mediates insulin resistance by tumor necrosis factor-alpha in brown adipocytes by maintaining Akt in an inactive dephosphorylated state. Diabetes 50, 2563-71
11679435   Curated Info

24

Adi S, Wu NY, Rosenthal SM (2001) Growth factor-stimulated phosphorylation of Akt and p70(S6K) is differentially inhibited by LY294002 and Wortmannin. Endocrinology 142, 498-501
11145615   Curated Info

25

Weng QP, et al. (1998) Regulation of the p70 S6 kinase by phosphorylation in vivo. Analysis using site-specific anti-phosphopeptide antibodies. J Biol Chem 273, 16621-9
9632736   Curated Info

26

Ferrari S, et al. (1992) Activation of p70s6k is associated with phosphorylation of four clustered sites displaying Ser/Thr-Pro motifs. Proc Natl Acad Sci U S A 89, 7282-6
1496022   Curated Info