Thr412
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Home > Phosphorylation Site Page: > Thr412  -  p70S6K (rat)

Site Information
NQVFLGFtYVAPSVL   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448607

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 37 ) , electrophoretic mobility shift ( 46 ) , immunoprecipitation ( 1 , 11 , 26 ) , mutation of modification site ( 1 , 16 , 42 , 43 , 47 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 47 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 30 , 31 , 33 , 34 , 35 , 37 , 38 , 39 , 41 , 42 , 46 , 47 )
Disease tissue studied:
HNSCC ( 2 )
Relevant cell line - cell type - tissue:
'brain, hippocampus' ( 20 ) , 'brain, striatum' ( 20 ) , 'muscle, skeletal' ( 5 , 12 , 14 , 22 , 24 , 26 , 27 , 28 , 35 , 36 , 38 , 40 ) , 'neuron, cortical'-brain ( 8 ) , 'neuron, hippocampal'-'brain, embryonic' ( 1 ) , 'neuron, hippocampal'-brain ( 8 ) , 293 (epithelial) ( 47 ) , 293T (epithelial) ( 16 ) , 3T3 (fibroblast) ( 7 ) , 3T3-L1 (fibroblast) ( 14 ) , adipocyte-adipose tissue ( 30 ) , artery-heart ( 45 ) , BHK-21 (fibroblast) ( 39 ) , C2C12 (myoblast) ( 13 ) , Cal27 (squamous) ( 2 ) , CHO (fibroblast) ( 14 ) , CHO (fibroblast) [EphB1 (human), transfection] ( 47 ) , CHO (fibroblast) [INSR (human), transfection] ( 42 ) , COS (fibroblast) ( 16 ) , Fao (hepatic) ( 14 ) , GEC (epithelial) ( 4 ) , granulosa ( 18 ) , H4IIe (hepatic) ( 37 ) , H9c2 (myoblast) ( 13 ) , heart ( 21 , 25 , 32 ) , HeLa (cervical) ( 14 ) , hepatocyte-liver ( 33 ) , IEC-18 (epithelial) ( 31 ) , L6 (myoblast) ( 7 , 9 , 14 , 46 ) , M059J (glial) ( 15 ) , MEF (fibroblast) ( 15 ) , myoblast ( 10 ) , myocardium ( 23 ) , myocyte-heart ( 11 , 17 , 41 ) , neuron-'brain, cerebral cortex' ( 16 ) , RAEC (endothelial) ( 19 ) , Rat1 (fibroblast) ( 15 , 43 ) , RIN (epithelial) ( 34 ) , sertoli-testis ( 29 ) , UMUC6 (bladder cell) ( 2 ) , VSMC ( 3 )

Upstream Regulation
Regulatory protein:
CAB39 (human) ( 17 ) , CDK5 (rat) ( 16 ) , EEA1 (human) ( 3 ) , FAK (rat) ( 11 ) , LKB1 (mouse) ( 17 ) , SHP-2 (rat) ( 11 ) , STRAD (human) ( 17 )
Putative in vivo kinases:
NEK6 (human) ( 44 ) , PDK1 (rat) ( 44 )
Kinases, in vitro:
mTOR (human) ( 48 ) , NEK6 (human) ( 44 )
Treatments:
acadesine ( 40 ) , actinomycin_D ( 46 ) , adrenalectomy ( 23 ) , amino_acids ( 33 , 35 ) , angiotensin_2 ( 3 ) , BAPTA-AM ( 8 ) , BDNF ( 1 , 8 ) , calyculin_A ( 37 ) , colforsin ( 39 ) , compound_401 ( 15 ) , CPCCOEt ( 20 ) , cyclic_stretch ( 11 ) , depolarization ( 8 ) , development ( 5 , 24 ) , dexamethasone ( 42 , 46 ) , DHPG ( 20 ) , EGTA ( 8 ) , ethanol ( 32 , 35 , 38 ) , exercise ( 36 ) , geldanamycin ( 46 ) , GLP-2 ( 39 ) , glucagon ( 33 ) , glucosamine ( 34 ) , glucose ( 4 ) , GW_8510 ( 16 ) , H2O2 ( 41 ) , hypoxia ( 19 ) , IGF-1 ( 22 , 38 ) , IgG ( 8 ) , indinavir ( 28 ) , insulin ( 7 , 9 , 10 , 16 , 23 , 27 , 28 , 29 , 30 , 33 , 34 , 37 , 42 , 44 , 47 ) , Intralipid ( 22 ) , ischemia/reperfusion ( 45 ) , K252a ( 8 ) , KN-62 ( 8 ) , KN-93 ( 8 ) , lapatinib ( 2 ) , leucine ( 12 , 22 ) , low_Ca(2+) ( 43 ) , LY294002 ( 2 , 8 , 15 , 29 , 44 ) , meal feeding ( 21 , 26 , 27 ) , mechanical stress ( 24 ) , metoprolol ( 23 ) , mifepristone ( 38 , 46 ) , MPEP ( 20 ) , NMDA ( 8 ) , okadaic_acid ( 33 ) , osmotic_stress ( 37 ) , palmitate ( 7 ) , paracetamol ( 5 ) , PDGF ( 15 ) , phenylephrine ( 15 , 43 ) , piclidenoson ( 25 ) , PKI-(14-22)amide ( 18 ) , PP2 ( 11 ) , PP242 ( 9 ) , rapamycin ( 1 , 4 , 8 , 9 , 15 , 16 , 18 , 19 , 29 , 30 , 41 , 46 , 47 ) , seliciclib ( 1 , 16 ) , sepsis ( 12 ) , serum ( 47 ) , serum_withdrawal ( 13 ) , testosterone ( 10 ) , TGF-beta ( 18 ) , U0126 ( 8 , 30 ) , U73122 ( 8 ) , urofollitropin ( 18 , 29 ) , vanadate ( 37 ) , W-13 ( 8 ) , wortmannin ( 18 , 30 , 37 , 41 , 44 , 47 ) , XeC ( 8 ) , Y27632 ( 13 )

Downstream Regulation
Effects of modification on p70S6K:
enzymatic activity, induced ( 16 , 29 , 41 , 42 , 44 , 47 )

Disease / Diagnostics Relevance
Relevant diseases:
diabetes mellitus ( 4 ) , type 2 diabetes ( 14 )

References 

1

Lai KO, et al. (2015) Cyclin-dependent Kinase 5 (Cdk5)-dependent Phosphorylation of p70 Ribosomal S6 Kinase 1 (S6K) Is Required for Dendritic Spine Morphogenesis. J Biol Chem 290, 14637-46
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2

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
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3

Nazarewicz RR, et al. (2011) Early endosomal antigen 1 (EEA1) is an obligate scaffold for angiotensin II-induced, PKC-alpha-dependent Akt activation in endosomes. J Biol Chem 286, 2886-95
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4

Mariappan MM, et al. (2011) Ribosomal biogenesis induction by high glucose requires activation of upstream binding factor in kidney glomerular epithelial cells. Am J Physiol Renal Physiol 300, F219-30
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5

Wu M, et al. (2010) Acetaminophen improves protein translational signaling in aged skeletal muscle. Rejuvenation Res 13, 571-9
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6

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
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7

Nascimento EB, et al. (2010) Phosphorylation of PRAS40 on Thr246 by PKB/AKT facilitates efficient phosphorylation of Ser183 by mTORC1. Cell Signal 22, 961-7
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8

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
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9

Feldman ME, et al. (2009) Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 7, e38
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10

Allemand MC, et al. (2009) Effect of testosterone on insulin stimulated IRS1 Ser phosphorylation in primary rat myotubes--a potential model for PCOS-related insulin resistance. PLoS One 4, e4274
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11

Marin TM, et al. (2008) Shp2 negatively regulates growth in cardiomyocytes by controlling focal adhesion kinase/Src and mTOR pathways. Circ Res 103, 813-24
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12

Vary TC (2007) Acute oral leucine administration stimulates protein synthesis during chronic sepsis through enhanced association of eukaryotic initiation factor 4G with eukaryotic initiation factor 4E in rats. J Nutr 137, 2074-9
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13

Lim MJ, et al. (2007) RhoA/Rho kinase blocks muscle differentiation via serine phosphorylation of insulin receptor substrate-1 and -2. Mol Endocrinol 21, 2282-93
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14

Tremblay F, et al. (2007) Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance. Proc Natl Acad Sci U S A 104, 14056-61
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15

Ballou LM, et al. (2007) Inhibition of mammalian target of rapamycin signaling by 2-(morpholin-1-yl)pyrimido[2,1-alpha]isoquinolin-4-one. J Biol Chem 282, 24463-70
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16

Hou Z, He L, Qi RZ (2007) Regulation of s6 kinase 1 activation by phosphorylation at ser-411. J Biol Chem 282, 6922-8
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17

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
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18

Chen YJ, et al. (2007) Interplay of PI3K and cAMP/PKA signaling, and rapamycin-hypersensitivity in TGFbeta1 enhancement of FSH-stimulated steroidogenesis in rat ovarian granulosa cells. J Endocrinol 192, 405-19
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19

Li W, et al. (2007) Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2. Circ Res 100, 79-87
17110594   Curated Info

20

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
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21

Vary TC, Lynch CJ (2006) Meal feeding stimulates phosphorylation of multiple effector proteins regulating protein synthetic processes in rat hearts. J Nutr 136, 2284-90
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22

Lang CH (2006) Elevated plasma free fatty acids decrease basal protein synthesis, but not the anabolic effect of leucine, in skeletal muscle. Am J Physiol Endocrinol Metab 291, E666-74
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23

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
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24

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

25

Park SS, et al. (2006) N6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide confers cardioprotection at reperfusion by inhibiting mitochondrial permeability transition pore opening via glycogen synthase kinase 3 beta. J Pharmacol Exp Ther 318, 124-31
16611852   Curated Info

26

Vary TC, Lynch CJ (2006) Meal feeding enhances formation of eIF4F in skeletal muscle: role of increased eIF4E availability and eIF4G phosphorylation. Am J Physiol Endocrinol Metab 290, E631-42
16263769   Curated Info

27

Vary TC, Goodman S, Kilpatrick LE, Lynch CJ (2005) Nutrient regulation of PKCepsilon is mediated by leucine, not insulin, in skeletal muscle. Am J Physiol Endocrinol Metab 289, E684-94
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28

Hong-Brown LQ, et al. (2005) Indinavir alters regulators of protein anabolism and catabolism in skeletal muscle. Am J Physiol Endocrinol Metab 289, E382-90
15827064   Curated Info

29

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

30

Hers I, Tavaré JM (2005) Mechanism of feedback regulation of insulin receptor substrate-1 phosphorylation in primary adipocytes. Biochem J 388, 713-20
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31

Chiu T, Santiskulvong C, Rozengurt E (2005) EGF receptor transactivation mediates ANG II-stimulated mitogenesis in intestinal epithelial cells through the PI3-kinase/Akt/mTOR/p70S6K1 signaling pathway. Am J Physiol Gastrointest Liver Physiol 288, G182-94
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32

Vary TC, Deiter G, Goodman SA (2005) Acute alcohol intoxication enhances myocardial eIF4G phosphorylation despite reducing mTOR signaling. Am J Physiol Heart Circ Physiol 288, H121-8
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33

Mothe-Satney I, et al. (2004) In rat hepatocytes glucagon increases mammalian target of rapamycin phosphorylation on serine 2448 but antagonizes the phosphorylation of its downstream targets induced by insulin and amino acids. J Biol Chem 279, 42628-37
15292249   Curated Info

34

Andreozzi F, et al. (2004) Activation of the hexosamine pathway leads to phosphorylation of insulin receptor substrate-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin insulin biosynthetic pathway in RIN pancreatic beta-cells. Endocrinology 145, 2845-57
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35

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
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36

Bolster DR, et al. (2003) Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle. J Physiol 553, 213-20
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37

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
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38

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
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39

Yusta B, Estall J, Drucker DJ (2002) Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase. J Biol Chem 277, 24896-906
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40

Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002) AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 277, 23977-80
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41

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
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42

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
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43

Ballou LM, et al. (2001) Dual regulation of glycogen synthase kinase-3beta by the alpha1A-adrenergic receptor. J Biol Chem 276, 40910-6
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44

Belham C, Comb MJ, Avruch J (2001) Identification of the NIMA family kinases NEK6/7 as regulators of the p70 ribosomal S6 kinase. Curr Biol 11, 1155-67
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45

Janelidze S, Hu BR, Siesjö P, Siesjö BK (2001) Alterations of Akt1 (PKBalpha) and p70(S6K) in transient focal ischemia. Neurobiol Dis 8, 147-54
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46

Shah OJ, Kimball SR, Jefferson LS (2000) Glucocorticoids abate p70(S6k) and eIF4E function in L6 skeletal myoblasts. Am J Physiol Endocrinol Metab 279, E74-82
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47

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
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48

Burnett PE, et al. (1998) RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci U S A 95, 1432-7
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