Ser32
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Home > Phosphorylation Site Page: > Ser32  -  IkB-alpha (mouse)

Site Information
LVDDRHDsGLDsMKD   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448203

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 1 ) , [32P] bio-synthetic labeling ( 26 ) , mutation of modification site ( 1 , 2 , 25 , 32 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 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 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 31 )
Disease tissue studied:
colorectal cancer ( 22 , 27 ) , colorectal carcinoma ( 22 , 27 ) , lung cancer ( 13 ) , lymphoma ( 29 ) , B cell lymphoma ( 29 )
Relevant cell line - cell type - tissue:
B lymphocyte-spleen ( 4 , 24 , 30 ) , BMMC (mast) ( 31 ) , bone marrow ( 23 ) , BV2 (microglia) ( 1 ) , C2C12 (myoblast) ( 12 ) , CMT-93 (intestinal) ( 22 , 27 ) , colon ( 8 , 19 ) , HEK293T (epithelial) ( 32 ) , liver ( 11 ) , lung ( 13 ) , macrophage-bone marrow ( 16 ) , macrophage-peritoneum ( 3 ) , MEF (fibroblast) ( 2 , 4 , 5 , 7 , 14 , 17 , 25 ) , MEF (fibroblast) [NFkB-p65 (mouse), homozygous knockout] ( 9 ) , microglia ( 1 , 15 ) , myeloid ( 16 ) , myocyte-heart ( 20 ) , natural killer cell-spleen ( 18 ) , osteoclast ( 16 ) , RAW 264 (macrophage) ( 26 , 28 ) , RAW 264.7 (macrophage) ( 6 ) , skin ( 21 ) , spleen ( 23 ) , T lymphocyte ( 10 ) , WEHI-231 (B lymphocyte) ( 29 )

Upstream Regulation
Regulatory protein:
EAR-2 (mouse) ( 10 ) , GSK3B (human) ( 7 ) , IKKG (mouse) ( 2 ) , IL-1RA (mouse) ( 2 ) , LYN (mouse) ( 31 ) , SH3BP2 (mouse) ( 16 ) , TSC2 (mouse) ( 17 )
Putative in vivo kinases:
IKKB (mouse) ( 2 )
Kinases, in vitro:
IKKA (mouse) ( 14 ) , IKKB (mouse) ( 2 ) , IKKE (mouse) ( 33 ) , MST1 (mouse) ( 1 )
Treatments:
15d-PGJ2 ( 22 ) , 2-AP ( 6 ) , [6]-gingerol ( 21 ) , AG17 ( 6 ) , AG490 ( 6 ) , anti-CD40 ( 23 ) , anti-IgM ( 24 ) , anti-LT(beta)R ( 14 ) , Aplidin ( 25 ) , bacterial infection ( 19 , 27 ) , benzo(a)pyrene ( 13 ) , beta-amyloid_42 ( 15 ) , bortezomib ( 19 ) , cycloheximide ( 9 ) , DNP ( 31 ) , EDA-A1 ( 29 ) , GM-CSF ( 18 ) , Go_6976 ( 24 ) , guanosine ( 15 ) , IFN-gamma ( 6 ) , IgE ( 31 ) , IKK-beta_inhibitor_IV ( 20 ) , IL-10 ( 23 ) , IL-1b ( 9 ) , IMD-0354 ( 20 ) , ionomycin ( 18 ) , LPS ( 3 , 9 , 18 , 20 , 22 , 23 , 27 , 28 ) , LY294002 ( 12 , 15 ) , M-CSF ( 16 ) , MMS ( 17 ) , MSP ( 28 ) , NTCU ( 13 ) , okadaic_acid ( 6 ) , partial_hepatectomy ( 11 ) , peptidoglycan ( 26 ) , phorbol_ester ( 18 , 21 ) , PIF ( 12 ) , pomegranate_wine ( 13 ) , SB203580 ( 15 , 21 ) , SC-514 ( 2 , 20 ) , TGF-beta ( 27 ) , TNF ( 5 , 9 , 14 , 15 ) , U0126 ( 15 ) , virus infection ( 7 )

Downstream Regulation
Effects of modification on IkB-alpha:
protein degradation ( 2 , 30 , 32 )
Effects of modification on biological processes:
autophagy, inhibited ( 2 )

References 

1

Zhao S, et al. (2016) Hippo/MST1 signaling mediates microglial activation following acute cerebral ischemia-reperfusion injury. Brain Behav Immun 55, 236-48
26721416   Curated Info

2

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

3

Liu X, et al. (2011) Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk. Nat Immunol 12, 416-24
21441935   Curated Info

4

Tokunaga F, et al. (2011) SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex. Nature 471, 633-6
21455180   Curated Info

5

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

6

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

7

Lei CQ, et al. (2010) Glycogen synthase kinase 3β regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1. Immunity 33, 878-89
21145761   Curated Info

8

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
20710027   Curated Info

9

Geng H, et al. (2009) Phosphorylation of NF-kappaB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination. EMBO Rep 10, 381-6
19270718   Curated Info

10

Hermann-Kleiter N, et al. (2008) The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity. Immunity 29, 205-16
18701084   Curated Info

11

Malato Y, et al. (2008) Hepatocyte-specific inhibitor-of-kappaB-kinase deletion triggers the innate immune response and promotes earlier cell proliferation during liver regeneration. Hepatology 47, 2036-50
18393321   Curated Info

12

Russell ST, Eley HL, Wyke SM, Tisdale MJ (2008) Involvement of phosphoinositide 3-kinase and Akt in the induction of muscle protein degradation by proteolysis-inducing factor. Biochem J 409, 751-9
17961125   Curated Info

13

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

14

Basak S, et al. (2007) A fourth IkappaB protein within the NF-kappaB signaling module. Cell 128, 369-81
17254973   Curated Info

15

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

16

Ueki Y, et al. (2007) Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 "cherubism" mice. Cell 128, 71-83
17218256   Curated Info

17

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

18

Bezbradica JS, et al. (2006) Granulocyte-macrophage colony-stimulating factor regulates effector differentiation of invariant natural killer T cells during thymic ontogeny. Immunity 25, 487-97
16949316   Curated Info

19

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

20

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

21

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

22

Ruiz PA, Kim SC, Sartor RB, Haller D (2004) 15-deoxy-delta12,14-prostaglandin J2-mediated ERK signaling inhibits gram-negative bacteria-induced RelA phosphorylation and interleukin-6 gene expression in intestinal epithelial cells through modulation of protein phosphatase 2A activity. J Biol Chem 279, 36103-11
15199053   Curated Info

23

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

24

Blois JT, et al. (2004) B cell receptor-induced cAMP-response element-binding protein activation in B lymphocytes requires novel protein kinase Cdelta. J Biol Chem 279, 30123-32
15138267   Curated Info

25

Cuadrado A, et al. (2004) JNK activation is critical for Aplidin-induced apoptosis. Oncogene 23, 4673-80
15122339   Curated Info

26

Chen BC, et al. (2004) Peptidoglycan induces nuclear factor-kappaB activation and cyclooxygenase-2 expression via Ras, Raf-1, and ERK in RAW 264.7 macrophages. J Biol Chem 279, 20889-97
15007072   Curated Info

27

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
12672795   Curated Info

28

Zhou YQ, Chen YQ, Fisher JH, Wang MH (2002) Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein inhibits inducible cyclooxygenase-2 expression in murine macrophages. J Biol Chem 277, 38104-10
12177064   Curated Info

29

Kayagaki N, et al. (2002) BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2. Immunity 17, 515-24
12387744   Curated Info

30

Saijo K, et al. (2002) Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha. J Exp Med 195, 1647-52
12070292   Curated Info

31

Kitaura J, et al. (2000) Akt-dependent cytokine production in mast cells. J Exp Med 192, 729-40
10974038   Curated Info

32

Shirane M, et al. (1999) Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and IkappaBepsilon mediated by the F-box protein FWD1. J Biol Chem 274, 28169-74
10497169   Curated Info

33

Shimada T, et al. (1999) IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases. Int Immunol 11, 1357-62
10421793   Curated Info

34

Van Antwerp DJ, Verma IM (1996) Signal-induced degradation of I(kappa)B(alpha): association with NF-kappaB and the PEST sequence in I(kappa)B(alpha) are not required. Mol Cell Biol 16, 6037-45
8887633   Curated Info