Ser235
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Phosphorylation Site Page:
Ser235 - S6 (rat)

Site Information
IAKRRRLsSLRASTS    SwissProt Entrez-Gene
Predicted information: Scansite
Orthologous residues: S6 (human): S235, S6 (mouse): S235, S6 (fruit fly): A234
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448092

In vivo Characterization
Methods used to characterize site in vivo: 2D analysis (27), [32P] bio-synthetic labeling (27, 28), mass spectrometry (8, 9, 10, 11), mutation of modification site (13), peptide sequencing (27), phospho-antibody (1, 5, 7, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24), phosphoamino acid analysis (27), phosphopeptide mapping (27, 28), western blotting (1, 5, 7, 12, 13, 14, 15, 16, 20, 21, 23, 24)
Disease tissue studied: adrenal cancer (8, 9, 10, 11), pheochromocytoma (8, 9, 10, 11), kidney cancer (7, 21)
Relevant cell line - cell type - tissue: 'muscle, skeletal' (5, 15, 16, 17, 19, 22, 23), 293T (epithelial) (13), CACL1-111 (renal) (21), CHO-K1 (fibroblast) (24), COS (fibroblast) (13), ELT-3 (7), hepatocyte-liver (28), IEC-18 (epithelial) (20), kidney (7), L6 (myoblast) (12), liver (27), MKOC1 (renal) (21), myocyte-heart (14), neuron-'brain, cerebral cortex' (13), neuron-'brain, hippocampus' (1), NR-22 (fibroblast) (21), PC-12 (chromaffin) (8, 9, 10, 11), sertoli-testis (18)

Controlled by
Regulatory protein: CAB39 (human) (14), CDK5 (rat) (13), LKB1 (mouse) (14), STRAD (human) (14)
Putative upstream kinases: Akt1 (rat) (20), Akt2 (rat) (20)
Kinases, in vitro: p70S6K (rat) (26), PKACA (cow) (28)
Treatments: acetaminophen (5), bicuculline (1), cAMP analog (18), cycloheximide (27), exercise (19, 22), forskolin (18), FSH (18), FTI277 (18), gabazine (1), H-89 (18), IGF-1 (15), indinavir (17), insulin (12, 17, 18, 24), Intralipid (15), leucine (15), lithium (24), LY294002 (18), PP242 (12), rapamycin (12, 18, 19, 21), SB415286 (24), siRNA (13), wortmannin (18)



References

1

Srivastava T, et al. (2012) Regulation of neuronal mRNA translation by CaM-kinase I phosphorylation of eIF4GII. J Neurosci 32, 5620-30
22514323   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

Van de Velde S, Hogan MF, Montminy M (2011) mTOR links incretin signaling to HIF induction in pancreatic beta cells. Proc Natl Acad Sci U S A 108, 16876-82
21949366   Curated Info

4

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

5

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

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
20484410   Curated Info

7

Short JD, et al. (2010) AMPK-mediated phosphorylation of murine p27 at T197 promotes binding of 14-3-3 proteins and increases p27 stability. Mol Carcinog 49, 429-39
20146253   Curated Info

8

(2009) CST Curation Set: 6823; Year: 2009; Biosample/Treatment: cell line, PC-12/forskolin; Disease: pheochromocytoma; SILAC: -; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-RRX(s/t)(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-PKA Substrate (RRXS/T) (100G7) Rabbit mAb Cat#: 9624, PTMScan(R) Phospho-PKA Substrate Motif (K/RK/RXS*/T*) Immunoaffinity Beads Cat#: 1984
Curated Info

9

(2009) CST Curation Set: 6822; Year: 2009; Biosample/Treatment: cell line, PC-12/untreated; Disease: pheochromocytoma; SILAC: -; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-RRX(s/t)(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-PKA Substrate (RRXS/T) (100G7) Rabbit mAb Cat#: 9624, PTMScan(R) Phospho-PKA Substrate Motif (K/RK/RXS*/T*) Immunoaffinity Beads Cat#: 1984
Curated Info

10

(2009) CST Curation Set: 6821; Year: 2009; Biosample/Treatment: cell line, PC-12/forskolin; Disease: pheochromocytoma; SILAC: -; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-RRX(s/t)(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-PKA Substrate (RRXS/T) (100G7) Rabbit mAb Cat#: 9624, PTMScan(R) Phospho-PKA Substrate Motif (K/RK/RXS*/T*) Immunoaffinity Beads Cat#: 1984
Curated Info

11

(2009) CST Curation Set: 6820; Year: 2009; Biosample/Treatment: cell line, PC-12/untreated; Disease: pheochromocytoma; SILAC: -; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-RRX(s/t)(phosphorylation) Antibody Used to Purify Peptides prior to MS2: Phospho-PKA Substrate (RRXS/T) (100G7) Rabbit mAb Cat#: 9624, PTMScan(R) Phospho-PKA Substrate Motif (K/RK/RXS*/T*) Immunoaffinity Beads Cat#: 1984
Curated Info

12

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

13

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

14

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

15

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

16

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

17

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

18

L├ęcureuil 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

19

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

20

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
15358595   Curated Info

21

Adachi H, et al. (2004) Niban gene is commonly expressed in the renal tumors: a new candidate marker for renal carcinogenesis. Oncogene 23, 3495-500
14990989   Curated Info

22

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
12937293   Curated Info

23

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

24

Wang X, et al. (2002) Evidence that the dephosphorylation of Ser(535) in the epsilon-subunit of eukaryotic initiation factor (eIF) 2B is insufficient for the activation of eIF2B by insulin. Biochem J 367, 475-81
12133000   Curated Info

25

Flotow H, Thomas G (1992) Substrate recognition determinants of the mitogen-activated 70K S6 kinase from rat liver. J Biol Chem 267, 3074-8
1737763   Curated Info

26

Ferrari S, et al. (1991) Mitogen-activated 70K S6 kinase. Identification of in vitro 40 S ribosomal S6 phosphorylation sites. J Biol Chem 266, 22770-5
1939282   Curated Info

27

Krieg J, Hofsteenge J, Thomas G (1988) Identification of the 40 S ribosomal protein S6 phosphorylation sites induced by cycloheximide. J Biol Chem 263, 11473-7
3403539   Curated Info

28

Wettenhall RE, Morgan FJ (1984) Phosphorylation of hepatic ribosomal protein S6 on 80 and 40 S ribosomes. Primary structure of S6 in the region of the major phosphorylation sites for cAMP-dependent protein kinases. J Biol Chem 259, 2084-91
6698958   Curated Info

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