Ser45
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Home > Phosphorylation Site Page: > Ser45  -  CTNNB1 (human)

Site Information
GATtTAPsLsGkGNP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447488

In vivo Characterization
Methods used to characterize site in vivo:
[32P] ATP in vitro ( 8 ) , [32P] bio-synthetic labeling ( 26 ) , immunoassay ( 7 , 15 ) , immunoprecipitation ( 6 , 8 , 9 , 12 , 17 , 18 ) , mass spectrometry ( 10 , 13 , 14 , 19 , 28 ) , mutation of modification site ( 6 , 9 , 12 , 22 , 24 , 25 , 26 , 28 , 30 ) , phospho-antibody ( 2 , 3 , 7 , 8 , 9 , 12 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 , 28 , 29 ) , western blotting ( 2 , 3 , 6 , 8 , 9 , 12 , 16 , 17 , 18 , 19 , 20 , 21 , 25 , 28 , 29 )
Disease tissue studied:
bone cancer ( 8 ) , breast cancer ( 2 , 13 , 18 , 21 ) , breast ductal carcinoma ( 2 , 13 ) , HER2 positive breast cancer ( 10 ) , luminal A breast cancer ( 10 ) , luminal B breast cancer ( 10 ) , breast cancer, triple negative ( 2 , 10 ) , colorectal cancer ( 6 , 16 , 19 , 25 ) , colorectal carcinoma ( 6 , 16 , 19 , 25 ) , kidney cancer ( 27 ) , Wilm's tumor ( 27 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
axin 1 (human) ( 28 ) , CK1A (human) ( 8 ) , HDAC6 (human) ( 20 ) , JNK1 (human) ( 17 ) , JNK2 (human) ( 17 ) , SMPD3 (human) ( 21 ) , WNT5A (human) ( 18 )
Putative in vivo kinases:
CK1A (rat) ( 18 , 29 ) , CK1E (human) ( 28 ) , IKKA (human) ( 26 )
Kinases, in vitro:
CK1A (human) ( 3 , 8 , 23 , 29 ) , CK1D (human) ( 28 ) , PKACA (human) ( 23 ) , PKCZ (human) ( 12 )
Putative upstream phosphatases:
PPP1CC (human) ( 21 )
Treatments:
anti-FGF19 ( 19 ) , C6-ceramide ( 21 ) , calyculin_A ( 21 ) , cAMP_analog ( 23 ) , CK1-7 ( 28 ) , CKI-7 ( 18 ) , H-89 ( 28 ) , high_cell_density ( 21 ) , lithium ( 28 , 29 ) , low_Ca(2+) ( 18 ) , MG132 ( 19 ) , mutation ( 20 ) , okadaic_acid ( 17 , 21 ) , olaparib ( 2 ) , siRNA ( 8 , 21 ) , SP600125 ( 17 ) , Wnt ( 29 ) , Wnt3a ( 28 )

Downstream Regulation
Effects of modification on CTNNB1:
intracellular localization ( 6 , 16 ) , molecular association, regulation ( 9 , 16 , 18 , 29 ) , phosphorylation ( 28 , 29 ) , protein degradation ( 2 , 6 , 12 , 22 , 28 , 29 ) , protein stabilization ( 9 ) , ubiquitination ( 9 )
Effects of modification on biological processes:
carcinogenesis, induced ( 7 ) , carcinogenesis, inhibited ( 6 ) , cell adhesion, altered ( 18 ) , cell differentiation, induced ( 7 ) , cell growth, inhibited ( 6 , 12 ) , cell motility, altered ( 18 ) , signaling pathway regulation ( 2 , 6 ) , transcription, induced ( 9 ) , transcription, inhibited ( 6 , 8 , 12 )
Induce interaction with:
CBLL1 (human) ( 16 ) , CDH1 (human) ( 18 ) , RNF4 (human) ( 9 ) , axin 1 (human) ( 29 )

Disease / Diagnostics Relevance
Relevant diseases:
colorectal cancer ( 29 ) , esophageal carcinoma ( 7 ) , HNSCC ( 15 ) , Wilm's tumor ( 27 )

References 

1

Kimura H, et al. (2021) The Dickkopf1 and FOXM1 positive feedback loop promotes tumor growth in pancreatic and esophageal cancers. Oncogene 40, 4486-4502
34117362   Curated Info

2

Zhu X, et al. (2021) Efficacy and mechanism of the combination of PARP and CDK4/6 inhibitors in the treatment of triple-negative breast cancer. J Exp Clin Cancer Res 40, 122
33832512   Curated Info

3

Nong J, et al. (2021) Phase separation of Axin organizes the β-catenin destruction complex. J Cell Biol 220
33651074   Curated Info

4

Yang W, et al. (2020) Presenilin1 exerts antiproliferative effects by repressing the Wnt/¿¿-catenin pathway in glioblastoma. Cell Commun Signal
32046730   Curated Info

5

Li H, et al. (2020) Z-Ajoene Inhibits Growth of Colon Cancer by Promotion of CK1¿¿ Dependent ¿¿-Catenin Phosphorylation. Molecules
32041324   Curated Info

6

Li Y, et al. (2020) Cas9 Mediated Correction of ¿¿-catenin Mutation and Restoring the Expression of Protein Phosphorylation in Colon Cancer HCT-116 Cells Decrease Cell Proliferation in vitro and Hamper Tumor Growth in Mice in vivo. Onco Targets Ther
32021251   Curated Info

7

Pan X, Ma L, Wang J (2019) Correlation between CK1¿¿ and ¿¿-catenin Ser45-phosphorylation in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol
31933784   Curated Info

8

Liu X, et al. (2019) Tumor-derived CK1α mutations enhance MDMX inhibition of p53. Oncogene
31462704   Curated Info

9

Thomas JJ, et al. (2016) RNF4-Dependent Oncogene Activation by Protein Stabilization. Cell Rep 16, 3388-400
27653698   Curated Info

10

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

11

Iaconelli J, et al. (2015) HDAC6 inhibitors modulate Lys49 acetylation and membrane localization of β-catenin in human iPSC-derived neuronal cells. ACS Chem Biol 10, 883-90
25546293   Curated Info

12

Llado V, et al. (2015) Repression of Intestinal Stem Cell Function and Tumorigenesis through Direct Phosphorylation of β-Catenin and Yap by PKCζ Cell Rep
25660024   Curated Info

13

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

14

Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7
23749302   Curated Info

15

Frederick MJ, et al. (2011) Phosphoproteomic analysis of signaling pathways in head and neck squamous cell carcinoma patient samples. Am J Pathol 178, 548-71
21281788   Curated Info

16

Maher MT, et al. (2010) Beta-catenin phosphorylated at serine 45 is spatially uncoupled from beta-catenin phosphorylated in the GSK3 domain: implications for signaling. PLoS One 5, e10184
20419129   Curated Info

17

Lee MH, Koria P, Qu J, Andreadis ST (2009) JNK phosphorylates beta-catenin and regulates adherens junctions. FASEB J 23, 3874-83
19667122   Curated Info

18

Medrek C, Landberg G, Andersson T, Leandersson K (2009) Wnt-5a-CKI{alpha} signaling promotes {beta}-catenin/E-cadherin complex formation and intercellular adhesion in human breast epithelial cells. J Biol Chem 284, 10968-79
19244247   Curated Info

19

Pai R, et al. (2008) Inhibition of fibroblast growth factor 19 reduces tumor growth by modulating beta-catenin signaling. Cancer Res 68, 5086-95
18593907   Curated Info

20

Li Y, et al. (2008) HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. J Biol Chem 283, 12686-90
18356165   Curated Info

21

Marchesini N, Jones JA, Hannun YA (2007) Confluence induced threonine41/serine45 phospho-beta-catenin dephosphorylation via ceramide-mediated activation of PP1cgamma. Biochim Biophys Acta 1771, 1418-28
17996206   Curated Info

22

Wu G, He X (2006) Threonine 41 in beta-catenin serves as a key phosphorylation relay residue in beta-catenin degradation. Biochemistry 45, 5319-23
16618120   Curated Info

23

Hino S, Tanji C, Nakayama KI, Kikuchi A (2005) Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination. Mol Cell Biol 25, 9063-72
16199882   Curated Info

24

Provost E, et al. (2005) Functional correlates of mutation of the Asp32 and Gly34 residues of beta-catenin. Oncogene 24, 2667-76
15829978   Curated Info

25

Wang Z, Vogelstein B, Kinzler KW (2003) Phosphorylation of beta-catenin at S33, S37, or T41 can occur in the absence of phosphorylation at T45 in colon cancer cells. Cancer Res 63, 5234-5
14500351   Curated Info

26

Provost E, et al. (2003) Functional correlates of mutations in beta-catenin exon 3 phosphorylation sites. J Biol Chem 278, 31781-9
12799363   Curated Info

27

Kusafuka T, et al. (2002) Codon 45 of the beta-catenin gene, a specific mutational target site of Wilms' tumor. Int J Mol Med 10, 395-9
12239584   Curated Info

28

Amit S, et al. (2002) Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev 16, 1066-76
12000790   Curated Info

29

Liu C, et al. (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108, 837-47
11955436   Curated Info

30

Morin PJ, et al. (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275, 1787-90
9065402   Curated Info