Thr36
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Home > Phosphorylation Site Page: > Thr36  -  4E-BP1 (rat)

Site Information
PPGDYsttPGGtLFS   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447497

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 3 , 18 ) , [32P] bio-synthetic labeling ( 17 , 18 , 19 , 21 ) , electrophoretic mobility shift ( 11 , 17 ) , mass spectrometry ( 1 , 2 ) , mutation of modification site ( 17 ) , phospho-antibody ( 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ) , phosphoamino acid analysis ( 18 ) , phosphopeptide mapping ( 17 , 18 , 21 ) , western blotting ( 3 , 4 , 5 , 6 , 7 , 8 , 11 , 12 , 13 , 14 )
Disease tissue studied:
breast cancer ( 6 ) , liver cancer ( 6 )
Relevant cell line - cell type - tissue:
'brain, cerebral cortex' ( 3 ) , 'brain, hippocampus' ( 3 ) , 'muscle, skeletal' ( 4 , 8 , 9 , 10 , 12 , 15 ) , 293 (epithelial) ( 13 , 14 , 17 ) , adipocyte-adipose tissue ( 18 , 19 , 21 ) , adipose tissue ( 2 ) , heart ( 2 ) , hepatocyte-liver ( 11 ) , IEC-18 (epithelial) ( 7 ) , intestine ( 2 ) , L6 (myoblast) ( 5 ) , liver ( 2 , 6 , 16 ) , lung ( 2 ) , mammary gland ( 6 ) , muscle ( 2 ) , pancreas ( 2 ) , PC-12 (chromaffin) [TrkA (rat), transfection] ( 1 ) , spleen ( 2 ) , stomach ( 2 ) , testis ( 2 ) , thymus ( 2 )

Upstream Regulation
Kinases, in vitro:
ERK2 (human) ( 20 , 21 ) , mTOR (rat) ( 20 )
Treatments:
acadesine ( 15 ) , amino_acids ( 11 , 12 , 17 ) , development ( 4 ) , ethanol ( 12 ) , exercise ( 10 ) , food deprivation ( 6 ) , glucagon ( 11 ) , H2O2 ( 4 ) , IGF-1 ( 8 ) , indinavir ( 9 ) , insulin ( 5 , 9 , 11 , 13 , 14 , 17 , 18 , 21 ) , Intralipid ( 8 ) , ischemia ( 3 ) , ischemia/reperfusion ( 3 ) , leucine ( 8 ) , paracetamol ( 4 ) , partial_hepatectomy ( 16 ) , phorbol_ester ( 7 ) , PP242 ( 5 ) , rapamycin ( 5 , 7 , 10 , 13 , 14 , 16 , 17 , 18 , 21 )

Downstream Regulation
Effects of modification on 4E-BP1:
molecular association, regulation ( 3 , 17 , 18 ) , phosphorylation ( 17 )
Effects of modification on biological processes:
translation, altered ( 3 , 17 )
Inhibit interaction with:
EIF4E (human) ( 17 ) , EIF4E (rat) ( 3 , 18 )

References 

1

Biarc J, Chalkley RJ, Burlingame AL, Bradshaw RA (2012) The induction of serine/threonine protein phosphorylations by a PDGFR/TrkA chimera in stably transfected PC12 cells. Mol Cell Proteomics 11, 15-30
22027198   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

Ayuso MI, et al. (2010) New hierarchical phosphorylation pathway of the translational repressor eIF4E-binding protein 1 (4E-BP1) in ischemia-reperfusion stress. J Biol Chem 285, 34355-63
20736160   Curated Info

4

Wu M, et al. (2010) Acetaminophen improves protein translational signaling in aged skeletal muscle. Rejuvenation Res 13, 571-9
20818934   Curated Info

5

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

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

Guan L, et al. (2007) Protein kinase C-mediated down-regulation of cyclin D1 involves activation of the translational repressor 4E-BP1 via a phosphoinositide 3-kinase/Akt-independent, protein phosphatase 2A-dependent mechanism in intestinal epithelial cells. J Biol Chem 282, 14213-25
17360714   Curated Info

8

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
16684854   Curated Info

9

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

10

Kubica N, et al. (2005) Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2Bepsilon mRNA in a mammalian target of rapamycin-dependent manner. J Biol Chem 280, 7570-80
15591312   Curated Info

11

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

12

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

13

Ferguson G, Mothe-Satney I, Lawrence JC (2003) Ser-64 and Ser-111 in PHAS-I are dispensable for insulin-stimulated dissociation from eIF4E. J Biol Chem 278, 47459-65
14507920   Curated Info

14

Beugnet A, Wang X, Proud CG (2003) Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1. J Biol Chem 278, 40717-22
12912989   Curated Info

15

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
11997383   Curated Info

16

Jiang YP, Ballou LM, Lin RZ (2001) Rapamycin-insensitive regulation of 4e-BP1 in regenerating rat liver. J Biol Chem 276, 10943-51
11278364   Curated Info

17

Mothe-Satney I, et al. (2000) Multiple mechanisms control phosphorylation of PHAS-I in five (S/T)P sites that govern translational repression. Mol Cell Biol 20, 3558-67
10779345   Curated Info

18

Heesom KJ, Avison MB, Diggle TA, Denton RM (1998) Insulin-stimulated kinase from rat fat cells that phosphorylates initiation factor 4E-binding protein 1 on the rapamycin-insensitive site (serine-111). Biochem J 336 ( Pt 1), 39-48
9806882   Curated Info

19

Fadden P, Haystead TA, Lawrence JC (1998) Phosphorylation of the translational regulator, PHAS-I, by protein kinase CK2. FEBS Lett 435, 105-9
9755868   Curated Info

20

Brunn GJ, Fadden P, Haystead TA, Lawrence JC (1997) The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-Pro motif and is activated by antibodies to a region near its COOH terminus. J Biol Chem 272, 32547-50
9405468   Curated Info

21

Fadden P, Haystead TA, Lawrence JC (1997) Identification of phosphorylation sites in the translational regulator, PHAS-I, that are controlled by insulin and rapamycin in rat adipocytes. J Biol Chem 272, 10240-7
9092573   Curated Info