Ser434
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Home > Phosphorylation Site Page: > Ser434  -  p70S6K (human)

Site Information
sFEPKIRsPRRFIGs   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448356

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 8 , 9 , 10 , 15 , 16 , 17 , 18 ) , mass spectrometry ( 17 ) , mutation of modification site ( 8 , 15 , 16 , 18 ) , peptide sequencing ( 15 , 17 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 14 ) , phosphoamino acid analysis ( 9 , 16 , 17 ) , phosphopeptide mapping ( 8 , 13 , 15 , 16 , 17 , 18 ) , western blotting ( 1 , 2 , 4 , 5 , 6 , 7 , 9 , 12 , 13 )
Disease tissue studied:
breast cancer ( 1 , 2 , 7 , 9 ) , colorectal cancer ( 4 ) , colorectal carcinoma ( 4 ) , ovarian cancer ( 9 ) , multiple myeloma ( 12 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
FRS2 (human) ( 2 ) , TSC1 (mouse) ( 6 ) , TSC2 (mouse) ( 6 )
Putative in vivo kinases:
CDK1 (human) ( 7 ) , mTOR (human) ( 3 )
Kinases, in vitro:
ERK1 (mouse) ( 14 ) , ERK2 (human) ( 12 ) , ERK2 (mouse) ( 14 ) , JNK1 (mouse) ( 14 ) , JNK2 (mouse) ( 14 )
Treatments:
bisindolylmaleimide ( 4 ) , EGF ( 4 , 14 ) , EGTA ( 8 ) , FGF1 ( 2 ) , FK506 ( 18 ) , heregulin ( 2 ) , IGF-1 ( 12 ) , IL-6 ( 12 ) , insulin ( 5 , 6 ) , LY294002 ( 1 , 3 ) , methylxanthine ( 18 ) , nocodazole ( 5 , 7 ) , PD98059 ( 4 , 7 , 12 , 14 ) , phorbol_ester ( 14 ) , purvalanol ( 7 ) , rapamycin ( 3 , 4 , 5 , 6 , 7 , 12 , 14 , 18 ) , SB202190 ( 7 , 14 ) , seliciclib ( 7 ) , serum ( 1 , 8 , 18 ) , taxol ( 5 , 9 ) , U0126 ( 1 , 4 , 7 , 12 ) , UV ( 14 ) , vanadate ( 7 ) , wortmannin ( 6 , 7 , 12 , 14 , 18 )

Downstream Regulation
Effects of modification on p70S6K:
enzymatic activity, induced ( 18 )

References 

1

Khau T, et al. (2011) Annexin-1 signals mitogen-stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2. FASEB J 25, 483-96
20930115   Curated Info

2

Manuvakhova M, et al. (2006) Expression of the SNT-1/FRS2 phosphotyrosine binding domain inhibits activation of MAP kinase and PI3-kinase pathways and antiestrogen resistant growth induced by FGF-1 in human breast carcinoma cells. Oncogene 25, 6003-14
16682955   Curated Info

3

Ali SM, Sabatini DM (2005) Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site. J Biol Chem 280, 19445-8
15809305   Curated Info

4

Sawhney RS, et al. (2004) Autocrine transforming growth factor alpha regulates cell adhesion by multiple signaling via specific phosphorylation sites of p70S6 kinase in colon cancer cells. J Biol Chem 279, 47379-90
15304500   Curated Info

5

Asnaghi L, et al. (2004) Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt. Oncogene 23, 5781-91
15208671   Curated Info

6

Shah OJ, Hunter T (2004) Critical role of T-loop and H-motif phosphorylation in the regulation of S6 kinase 1 by the tuberous sclerosis complex. J Biol Chem 279, 20816-23
14993219   Curated Info

7

Shah OJ, Ghosh S, Hunter T (2003) Mitotic regulation of ribosomal S6 kinase 1 involves Ser/Thr, Pro phosphorylation of consensus and non-consensus sites by Cdc2. J Biol Chem 278, 16433-42
12586835   Curated Info

8

Hannan KM, Thomas G, Pearson RB (2003) Activation of S6K1 (p70 ribosomal protein S6 kinase 1) requires an initial calcium-dependent priming event involving formation of a high-molecular-mass signalling complex. Biochem J 370, 469-77
12429015   Curated Info

9

Le XF, et al. (2003) Paclitaxel induces inactivation of p70 S6 kinase and phosphorylation of Thr421 and Ser424 via multiple signaling pathways in mitosis. Oncogene 22, 484-97
12555062   Curated Info

10

Neri LM, et al. (2003) The phosphoinositide 3-kinase/AKT1 pathway involvement in drug and all-trans-retinoic acid resistance of leukemia cells. Mol Cancer Res 1, 234-46
12556562   Curated Info

11

Bettoun DJ, et al. (2002) A vitamin D receptor-Ser/Thr phosphatase-p70 S6 kinase complex and modulation of its enzymatic activities by the ligand. J Biol Chem 277, 24847-50
12036952   Curated Info

12

Shi Y, et al. (2002) Signal pathways involved in activation of p70S6K and phosphorylation of 4E-BP1 following exposure of multiple myeloma tumor cells to interleukin-6. J Biol Chem 277, 15712-20
11872747   Curated Info

13

Gonzalez-Garcia A, et al. (2002) A new role for the p85-phosphatidylinositol 3-kinase regulatory subunit linking FRAP to p70 S6 kinase activation. J Biol Chem 277, 1500-8
11684675   Curated Info

14

Zhang Y, et al. (2001) Signal transduction pathways involved in phosphorylation and activation of p70S6K following exposure to UVA irradiation. J Biol Chem 276, 20913-23
11279232   Curated Info

15

Moser BA, et al. (1997) Dual requirement for a newly identified phosphorylation site in p70s6k. Mol Cell Biol 17, 5648-55
9271440   Curated Info

16

Jefferies HB, et al. (1997) Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k. EMBO J 16, 3693-704
9218810   Curated Info

17

Pearson RB, et al. (1995) The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain. EMBO J 14, 5279-87
7489717   Curated Info

18

Han JW, Pearson RB, Dennis PB, Thomas G (1995) Rapamycin, wortmannin, and the methylxanthine SQ20006 inactivate p70s6k by inducing dephosphorylation of the same subset of sites. J Biol Chem 270, 21396-403
7545671   Curated Info