Ser534
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Home > Phosphorylation Site Page: > Ser534  -  NFkB-p65 (mouse)

Site Information
sGDEDFssIADMDFS   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447800

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 33 ) , immunoprecipitation ( 6 ) , mass spectrometry ( 3 ) , mutation of modification site ( 6 , 14 , 19 , 23 , 33 , 35 ) , phospho-antibody ( 1 , 2 , 5 , 6 , 7 , 8 , 9 , 13 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ) , western blotting ( 1 , 2 , 5 , 6 , 7 , 8 , 9 , 13 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 36 , 37 , 38 )
Disease tissue studied:
breast cancer ( 2 ) , colorectal cancer ( 38 ) , colorectal carcinoma ( 38 ) , kidney cancer ( 20 ) , leukemia ( 22 ) , acute myelogenous leukemia ( 22 ) , lung cancer ( 14 , 25 ) , melanoma skin cancer ( 17 ) , X-linked agammaglobulinaemia ( 22 )
Relevant cell line - cell type - tissue:
'brain, cerebral cortex' ( 31 ) , 'brain, striatum' ( 31 ) , 293 (epithelial) ( 8 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 34 ) , A549 (pulmonary) ( 14 ) , bladder ( 24 ) , bone marrow ( 27 , 37 ) , CMT-93 (intestinal) ( 38 ) , colon ( 1 , 16 , 30 ) , fibroblast-embryo ( 19 ) , HaCaT (keratinocyte) ( 5 ) , HEK293T (epithelial) ( 3 , 33 ) , keratinocyte-skin ( 7 ) , kidney ( 8 ) , kidney [PPM1D (mouse), homozygous knockout] ( 20 ) , liver ( 6 ) , lung ( 25 ) , lung [PPM1D (mouse), homozygous knockout] ( 20 ) , macrophage-peritoneum ( 35 ) , MDA-MB-231 (breast cell) ( 2 ) , MEF (fibroblast) ( 6 , 13 , 23 , 28 , 29 ) , MEF (fibroblast) [IGF1R (mouse)] ( 33 , 34 , 35 ) , MEF (fibroblast) [IKKE (mouse), homozygous knockout] ( 14 ) , melanocyte-skin [IKKB (mouse), homozygous knockout] ( 17 ) , microglia ( 26 ) , mononuclear ( 22 ) , myocyte-heart ( 32 ) , RAW 264.7 (macrophage) ( 15 , 21 ) , skin ( 5 , 36 ) , spleen ( 37 ) , THP1 (myeloid) ( 22 )

Upstream Regulation
Regulatory protein:
Akt1 (human) ( 19 ) , Btk (mouse) ( 22 ) , CARD9 (mouse) ( 9 ) , dectin-1 (mouse) ( 9 ) , GPX1 (mouse) ( 31 ) , IKKB (mouse) ( 17 ) , IKKE (mouse) ( 28 ) , ILK (mouse) ( 1 ) , MIEN1 (human) ( 2 ) , MKK6 (mouse) ( 27 ) , RGN (mouse) ( 8 ) , TAK1 (mouse) ( 27 ) , TSC2 (mouse) ( 29 )
Putative in vivo kinases:
IKKA (mouse) ( 19 , 33 , 35 ) , IKKB (mouse) ( 19 , 33 ) , IKKE (human) ( 28 )
Kinases, in vitro:
IKKA (human) ( 19 ) , IKKA (mouse) ( 33 ) , IKKB (human) ( 6 , 19 ) , IKKB (mouse) ( 33 )
Putative upstream phosphatases:
PPM1D (mouse) ( 20 )
Treatments:
4-HT ( 7 ) , [6]-gingerol ( 36 ) , aurentiacin ( 12 ) , bacterial infection ( 16 , 30 , 38 ) , benzo(a)pyrene ( 25 ) , beta-amyloid_42 ( 26 ) , bortezomib ( 30 ) , calyculin_A ( 32 ) , cpd22 ( 1 ) , CpG ( 22 ) , curdlan ( 9 ) , GSK-3_inhibitor_X ( 15 ) , guanosine ( 26 ) , IFN-gamma ( 15 ) , IKK-beta_inhibitor_IV ( 32 ) , IL-10 ( 37 ) , IL-1b ( 7 , 28 ) , IL-8 ( 33 ) , IMD-0354 ( 32 ) , ischemia ( 31 ) , licochalcone_A ( 21 ) , licochalcone_B ( 21 ) , licochalcone_C ( 21 ) , licochalcone_D ( 21 ) , LPS ( 12 , 21 , 28 , 32 , 35 , 37 , 38 ) , MMS ( 29 ) , NSC-87877 ( 15 ) , NTCU ( 25 ) , OH-BBN ( 24 ) , phorbol_ester ( 28 , 36 ) , pomegranate_wine ( 25 ) , RANKL ( 27 ) , resiquimod ( 22 ) , SB203580 ( 27 , 36 ) , SC-514 ( 32 ) , silibinin ( 24 ) , silymarin ( 24 ) , skin aging ( 5 ) , TGF-beta ( 38 ) , TNF ( 7 , 13 , 23 , 26 , 28 , 29 , 33 , 34 ) , UVB ( 5 ) , virus infection ( 14 )

Downstream Regulation
Effects of modification on NFkB-p65:
activity, induced ( 19 , 27 , 33 ) , molecular association, regulation ( 16 , 33 ) , protein degradation ( 6 , 35 ) , protein processing ( 33 )
Effects of modification on biological processes:
carcinogenesis, induced ( 19 ) , signaling pathway regulation ( 6 ) , transcription, altered ( 27 ) , transcription, induced ( 19 , 23 , 33 ) , transcription, inhibited ( 6 )
Induce interaction with:
p300 (mouse) ( 33 ) , p90RSK (mouse) ( 16 )
Inhibit interaction with:
DNA ( 6 )

References 

1

Ahmed AU, et al. (2017) Integrin-Linked Kinase Expression in Myeloid Cells Promotes Inflammatory Signaling during Experimental Colitis. J Immunol
28794235   Curated Info

2

Wang Y, et al. (2017) Inhibition of MAPK pathway is essential for suppressing Rheb-Y35N driven tumor growth. Oncogene 36, 756-765
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3

Meng J, et al. (2016) Breakpoint Cluster Region-Mediated Inflammation Is Dependent on Casein Kinase II. J Immunol 197, 3111-3119
27630163   Curated Info

4

Gagné-Sansfaçon J, et al. (2016) SHP-2 phosphatase contributes to KRAS-driven intestinal oncogenesis but prevents colitis-associated cancer development. Oncotarget 7, 65676-65695
27582544   Curated Info

5

Choi YJ, et al. (2016) The underlying mechanism of proinflammatory NF-κB activation by the mTORC2/Akt/IKKα pathway during skin aging. Oncotarget 7, 52685-52694
27486771   Curated Info

6

Pradère JP, et al. (2016) Negative regulation of NF-κB p65 activity by serine 536 phosphorylation. Sci Signal 9, ra85
27555662   Curated Info

7

Hayashi K, et al. (2015) Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA. Oncogene 34, 4647-55
25486434   Curated Info

8

Jung KJ, et al. (2015) Anti-inflammatory activity of SMP30 modulates NF-κB through protein tyrosine kinase/phosphatase balance. J Mol Med (Berl) 93, 343-56
25394676   Curated Info

9

Baldwin KT, Carbajal KS, Segal BM, Giger RJ (2015) Neuroinflammation triggered by β-glucan/dectin-1 signaling enables CNS axon regeneration. Proc Natl Acad Sci U S A 112, 2581-6
25675510   Curated Info

10

Chiang HS, et al. (2014) GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses. Nat Immunol 15, 63-71
24270516   Curated Info

11

Schröfelbauer B, et al. (2012) NEMO Ensures Signaling Specificity of the Pleiotropic IKKβ by Directing Its Kinase Activity toward IκBα. Mol Cell 47, 111-21
22633953   Curated Info

12

Kim YJ, et al. (2012) Inhibitory effects of aurentiacin from Syzygium samarangense on lipopolysaccharide-induced inflammatory response in mouse macrophages. Food Chem Toxicol 50, 1027-35
22155221   Curated Info

13

Ju J, et al. (2010) Phosphorylation of p50 NF-kappaB at a single serine residue by DNA-dependent protein kinase is critical for VCAM-1 expression upon TNF treatment. J Biol Chem 285, 41152-60
20966071   Curated Info

14

Bao X, et al. (2010) IKKε modulates RSV-induced NF-κB-dependent gene transcription. Virology 408, 224-31
20961594   Curated Info

15

Kai JI, et al. (2010) Glycogen synthase kinase-3β indirectly facilitates interferon-γ-induced nuclear factor-κB activation and nitric oxide biosynthesis. J Cell Biochem 111, 1522-30
20872791   Curated Info

16

Chandrakesan P, et al. (2010) Novel changes in NF-{kappa}B activity during progression and regression phases of hyperplasia: role of MEK, ERK, and p38. J Biol Chem 285, 33485-98
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17

Yang J, et al. (2010) Conditional ablation of Ikkb inhibits melanoma tumor development in mice. J Clin Invest 120, 2563-74
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18

Rajendrasozhan S, et al. (2010) Targeted disruption of NF-{kappa}B1 (p50) augments cigarette smoke-induced lung inflammation and emphysema in mice: a critical role of p50 in chromatin remodeling. Am J Physiol Lung Cell Mol Physiol 298, L197-209
19965984   Curated Info

19

Bai D, Ueno L, Vogt PK (2009) Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt. Int J Cancer 125, 2863-70
19609947   Curated Info

20

Chew J, et al. (2009) WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat Cell Biol 11, 659-66
19377466   Curated Info

21

Furusawa J, et al. (2009) Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit phosphorylation of NF-kappaB p65 in LPS signaling pathway. Int Immunopharmacol 9, 499-507
19291859   Curated Info

22

Doyle SL, Jefferies CA, Feighery C, O'Neill LA (2007) Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem 282, 36953-60
17932028   Curated Info

23

Sasaki CY, et al. (2007) Traf1 induction and protection from tumor necrosis factor by nuclear factor-kappaB p65 is independent of serine 536 phosphorylation. Cancer Res 67, 11218-25
18056447   Curated Info

24

Tyagi A, et al. (2007) Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine induced urinary bladder carcinogenesis in male ICR mice. Mol Cancer Ther 6, 3248-55
18089718   Curated Info

25

Khan N, et al. (2007) Oral consumption of pomegranate fruit extract inhibits growth and progression of primary lung tumors in mice. Cancer Res 67, 3475-82
17389758   Curated Info

26

D'Alimonte I, et al. (2007) Guanosine inhibits CD40 receptor expression and function induced by cytokines and beta amyloid in mouse microglia cells. J Immunol 178, 720-31
17202332   Curated Info

27

Huang H, et al. (2006) Osteoclast differentiation requires TAK1 and MKK6 for NFATc1 induction and NF-kappaB transactivation by RANKL. Cell Death Differ 13, 1879-91
16498455   Curated Info

28

Adli M, Baldwin AS (2006) IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via regulation of Ser-536 p65/RelA phosphorylation. J Biol Chem 281, 26976-84
16840782   Curated Info

29

Ghosh S, et al. (2006) Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-kappaB activation and cell survival. Cancer Cell 10, 215-26
16959613   Curated Info

30

Wang Y, Xiang GS, Kourouma F, Umar S (2006) Citrobacter rodentium-induced NF-kappaB activation in hyperproliferating colonic epithelia: role of p65 (Ser536) phosphorylation. Br J Pharmacol 148, 814-24
16751795   Curated Info

31

Crack PJ, et al. (2006) Potential contribution of NF-kappaB in neuronal cell death in the glutathione peroxidase-1 knockout mouse in response to ischemia-reperfusion injury. Stroke 37, 1533-8
16627788   Curated Info

32

Hall G, et al. (2005) Inhibitor-kappaB kinase-beta regulates LPS-induced TNF-alpha production in cardiac myocytes through modulation of NF-kappaB p65 subunit phosphorylation. Am J Physiol Heart Circ Physiol 289, H2103-11
15980040   Curated Info

33

Chen LF, et al. (2005) NF-kappaB RelA phosphorylation regulates RelA acetylation. Mol Cell Biol 25, 7966-75
16135789   Curated Info

34

Das S, et al. (2005) Tpl2/cot signals activate ERK, JNK, and NF-kappaB in a cell-type and stimulus-specific manner. J Biol Chem 280, 23748-57
15833743   Curated Info

35

Lawrence T, et al. (2005) IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation. Nature 434, 1138-43
15858576   Curated Info

36

Kim SO, et al. (2005) [6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-kappaB in phorbol ester-stimulated mouse skin. Oncogene 24, 2558-67
15735738   Curated Info

37

Bhattacharyya S, et al. (2004) Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkappaB kinase activity. Blood 104, 1100-9
15113757   Curated Info

38

Haller D, et al. (2003) Transforming growth factor-beta 1 inhibits non-pathogenic Gram negative bacteria-induced NF-kappa B recruitment to the interleukin-6 gene promoter in intestinal epithelial cells through modulation of histone acetylation. J Biol Chem 278, 23851-60
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