Ser177
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Home > Phosphorylation Site Page: > Ser177  -  IKKB (human)

Site Information
AkELDQGsLCtsFVG   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447492

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 20 , 22 ) , immunoprecipitation ( 1 , 11 , 12 ) , mass spectrometry ( 1 ) , mutation of modification site ( 1 , 5 , 15 , 16 , 18 , 20 , 22 , 24 ) , phospho-antibody ( 1 , 2 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ) , phosphopeptide mapping ( 22 ) , western blotting ( 1 , 2 , 5 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 24 )
Disease tissue studied:
cervical cancer ( 9 ) , cervical squamous cell carcinoma ( 9 ) , endometrial cancer ( 16 ) , endometrial adenocarcinoma ( 16 ) , liver cancer ( 15 ) , lung cancer ( 14 ) , non-small cell lung cancer ( 14 ) , fibrosarcoma of soft tissue ( 1 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
EGFR (human) ( 2 ) , LYN (human) ( 2 ) , MEKK3 (human) ( 11 ) , PPP2CA (human) ( 9 , 10 ) , Src (human) ( 9 )
Putative in vivo kinases:
AMPKA2 (human) ( 8 ) , Nik (human) ( 22 ) , PKCE (human) ( 7 )
Kinases, in vitro:
AMPKA2 (human) ( 8 ) , PKCA (human) ( 23 ) , PKCZ (human) ( 23 )
Putative upstream phosphatases:
PPM1B (human) ( 12 ) , PPPM1A (human) ( 12 )
Treatments:
Akt-I-1 ( 9 ) , angiotensin_2 ( 15 ) , bortezomib ( 16 ) , calyculin_A ( 9 ) , EGF ( 2 ) , herbimycin_A ( 9 ) , HGF ( 5 ) , IL-1b ( 9 ) , ionomycin ( 10 ) , L-glutamine_withdrawal ( 1 ) , LPA ( 10 ) , LPS ( 2 ) , LY294002 ( 9 ) , MG132 ( 9 ) , PD98059 ( 9 ) , phorbol_ester ( 5 , 10 ) , seliciclib ( 14 ) , SP600125 ( 9 ) , TNF ( 1 , 12 , 14 , 22 ) , vanadate ( 9 )

Downstream Regulation
Effects of modification on IKKB:
enzymatic activity, induced ( 4 , 7 , 12 , 20 , 22 , 24 ) , intracellular localization ( 24 ) , molecular association, regulation ( 24 )
Effects of modification on biological processes:
transcription, induced ( 12 )
Induce interaction with:
IKKA (human) ( 24 )

References 

1

Reid MA, et al. (2016) IKKβ promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3. Genes Dev 30, 1837-51
27585591   Curated Info

2

De S, et al. (2015) Erlotinib protects against LPS-induced Endotoxicity because TLR4 needs EGFR to signal. Proc Natl Acad Sci U S A 112, 9680-5
26195767   Curated Info

3

Gallo LH, et al. (2014) Novel Lys63-linked ubiquitination of IKKβ induces STAT3 signaling. Cell Cycle 13, 3964-76
25486864   Curated Info

4

Shinohara H, et al. (2014) Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation. Science 344, 760-4
24833394   Curated Info

5

Magliozzi R, et al. (2013) Control of Epithelial Cell Migration and Invasion by the IKKβ- and CK1α-Mediated Degradation of RAPGEF2. Dev Cell 27, 574-85
24290981   Curated Info

6

Meyer AN, et al. (2013) Tyrosine phosphorylation allows integration of multiple signaling inputs by IKKβ. PLoS One 8, e84497
24386391   Curated Info

7

Yang W, et al. (2012) EGFR-induced and PKCε monoubiquitylation-dependent NF-κB activation upregulates PKM2 expression and promotes tumorigenesis. Mol Cell 48, 771-84
23123196   Curated Info

8

Bess E, Fisslthaler B, Frömel T, Fleming I (2011) Nitric oxide-induced activation of the AMP-activated protein kinase α2 subunit attenuates IκB kinase activity and inflammatory responses in endothelial cells. PLoS One 6, e20848
21673972   Curated Info

9

Barisic S, Schmidt C, Walczak H, Kulms D (2010) Tyrosine phosphatase inhibition triggers sustained canonical serine-dependent NFkappaB activation via Src-dependent blockade of PP2A. Biochem Pharmacol 80, 439-47
20450893   Curated Info

10

Sun W, et al. (2010) Protein phosphatase 2A acts as a mitogen-activated protein kinase kinase kinase 3 (MEKK3) phosphatase to inhibit lysophosphatidic acid-induced IkappaB kinase beta/nuclear factor-kappaB activation. J Biol Chem 285, 21341-8
20448038   Curated Info

11

Sun W, et al. (2010) Phosphorylation of Thr-516 and Ser-520 in the kinase activation loop of MEKK3 is required for lysophosphatidic acid-mediated optimal IkappaB kinase beta (IKKbeta)/nuclear factor-kappaB (NF-kappaB) activation. J Biol Chem 285, 7911-8
20068038   Curated Info

12

Sun W, et al. (2009) PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation. Cell Signal 21, 95-102
18930133   Curated Info

13

Chen RA, et al. (2008) Inhibition of IkappaB kinase by vaccinia virus virulence factor B14. PLoS Pathog 4, e22
18266467   Curated Info

14

Dey A, et al. (2008) R-Roscovitine simultaneously targets both the p53 and NF-kappaB pathways and causes potentiation of apoptosis: implications in cancer therapy. Cell Death Differ 15, 263-73
17975552   Curated Info

15

Choudhary S, Lu M, Cui R, Brasier AR (2007) Involvement of a novel Rac/RhoA guanosine triphosphatase-nuclear factor-kappaB inducing kinase signaling pathway mediating angiotensin II-induced RelA transactivation. Mol Endocrinol 21, 2203-17
17595324   Curated Info

16

Dolcet X, et al. (2006) Proteasome inhibitors induce death but activate NF-kappaB on endometrial carcinoma cell lines and primary culture explants. J Biol Chem 281, 22118-30
16735506   Curated Info

17

Carter RS, et al. (2005) Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its phosphorylation and persistent activation. J Biol Chem 280, 43272-9
16267042   Curated Info

18

Carter RS, et al. (2003) Signal-induced ubiquitination of I kappaB Kinase-beta. J Biol Chem 278, 48903-6
14514672   Curated Info

19

Wang C, et al. (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-51
11460167   Curated Info

20

Carter RS, et al. (2001) Persistent activation of NF-kappa B by the tax transforming protein involves chronic phosphorylation of IkappaB kinase subunits IKKbeta and IKKgamma. J Biol Chem 276, 24445-8
11325957   Curated Info

21

Huynh QK, et al. (2000) Characterization of the recombinant IKK1/IKK2 heterodimer. Mechanisms regulating kinase activity. J Biol Chem 275, 25883-91
10823818   Curated Info

22

Delhase M, Hayakawa M, Chen Y, Karin M (1999) Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science 284, 309-13
10195894   Curated Info

23

Lallena MJ, et al. (1999) Activation of IkappaB kinase beta by protein kinase C isoforms. Mol Cell Biol 19, 2180-8
10022904   Curated Info

24

Mercurio F, et al. (1997) IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 278, 860-6
9346484   Curated Info