Ser33
Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage PhosphoSitePlus® v6.6.0.2
Powered by Cell Signaling Technology
Home > Phosphorylation Site Page: > Ser33  -  CTNNB1 (human)

Site Information
QQQsyLDsGIHsGAT   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447487

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 52 ) , immunoprecipitation ( 12 , 13 , 18 , 22 , 24 , 35 , 37 , 38 ) , mass spectrometry ( 27 , 30 , 40 , 46 , 56 ) , mutation of modification site ( 10 , 15 , 18 , 24 , 28 , 33 , 36 , 41 , 42 , 43 , 44 , 49 , 51 , 52 , 54 , 55 , 56 , 58 , 60 ) , phospho-antibody ( 4 , 5 , 6 , 10 , 11 , 12 , 13 , 14 , 15 , 18 , 20 , 22 , 25 , 26 , 29 , 31 , 32 , 33 , 34 , 35 , 37 , 38 , 39 , 40 , 42 , 43 , 45 , 47 , 48 , 49 , 50 , 51 , 53 , 54 , 55 , 56 , 57 , 58 ) , western blotting ( 4 , 5 , 6 , 10 , 11 , 12 , 13 , 14 , 15 , 18 , 20 , 22 , 24 , 25 , 26 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 42 , 43 , 47 , 50 , 51 , 53 , 54 , 55 , 56 , 57 , 58 )
Disease tissue studied:
bone cancer ( 33 ) , breast cancer ( 4 , 15 , 37 , 55 ) , breast ductal carcinoma ( 4 ) , breast cancer, triple negative ( 4 ) , chondrosarcoma ( 25 ) , colorectal cancer ( 6 , 10 , 24 , 31 , 34 , 39 , 40 , 51 , 54 ) , colorectal carcinoma ( 6 , 10 , 24 , 31 , 34 , 39 , 40 , 51 , 54 ) , gastric cancer ( 27 , 38 ) , gastric carcinoma ( 27 , 38 ) , kidney cancer ( 32 ) , leukemia ( 43 ) , chronic myelogenous leukemia ( 43 ) , lung cancer ( 30 ) , non-small cell lung cancer ( 30 ) , non-small cell squamous cell lung carcinoma ( 30 ) , ovarian cancer ( 46 ) , pancreatic cancer ( 14 ) , pancreatic carcinoma ( 14 ) , prostate cancer ( 26 ) , melanoma skin cancer ( 20 , 46 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 10 , 11 , 12 , 22 , 47 , 48 , 56 ) , 3Y1 (fibroblast) ( 42 ) , 4T1 (breast cell) ( 37 ) , A375 (melanocyte) ( 20 ) , A431 (epithelial) ( 35 ) , A498 (renal) [SFRP2 (human), transfection] ( 32 ) , AGS (gastric) ( 38 ) , BC-1 (B lymphocyte) ( 43 ) , C57MG (epithelial) ( 36 ) , Caco-2 (intestinal) ( 24 ) , Capan1 (pancreatic) ( 14 ) , CD18/HPAF (pancreatic) ( 14 ) , CHO (fibroblast) ( 58 ) , COS (fibroblast) ( 41 , 42 , 47 , 52 , 55 ) , COV413 (ovarian) ( 46 ) , DLD1 (intestinal) ( 39 ) , DM331 (melanocyte) ( 46 ) , endothelial-vein ( 53 ) , HCC1937 (breast cell) ( 4 ) , HCT116 (intestinal) ( 6 , 10 , 31 , 40 , 54 ) , HEK293T (epithelial) ( 5 , 24 , 31 , 39 , 54 , 55 , 58 , 59 ) , HeLa (cervical) ( 12 , 13 , 56 , 59 ) , HFFF-2 (fibroblast) ( 42 ) , HT-29 (intestinal) ( 45 , 54 ) , Jurkat (T lymphocyte) ( 50 , 56 ) , keratinocyte ( 28 ) , KU812 (myeloid) ( 43 ) , L3.6p1 (pancreatic) ( 14 ) , L929 (fibroblast) ( 56 ) , LNCaP (prostate cell) ( 26 ) , Ls174T (intestinal) ( 51 ) , MCF-7 (breast cell) ( 15 , 37 ) , MDA-MB-436 (breast cell) ( 4 ) , MDCK (epithelial) ( 49 , 54 ) , MEF (fibroblast) [axin 2 (mouse), homozygous knockout] ( 33 ) , mesangial ( 29 ) , MKN-45 (gastric) ( 27 ) , MKN-74 (gastric) ( 38 ) , NCI-H520 (squamous) ( 30 ) , oocyte ( 57 ) , Rat2 (fibroblast) ( 57 ) , RCS (chondrocyte) ( 25 ) , SKBr3 (breast cell) ( 55 ) , SLM2 (melanocyte) ( 46 ) , SNU16Ad (gastric) ( 38 ) , SUM149 (breast cell) ( 4 ) , SUM159 (breast cell) ( 15 ) , SW48 (intestinal) ( 60 ) , SW480 (intestinal) ( 31 , 34 , 54 ) , SW620 (intestinal) ( 31 ) , T lymphocyte-blood ( 44 ) , U2OS (bone cell) ( 33 )

Upstream Regulation
Regulatory protein:
APC (human) ( 22 ) , AurA (human) ( 38 ) , axin 1 (human) ( 5 , 56 ) , CDH2 (human) ( 54 ) , CTNNA1 (human) ( 22 ) , CTNNB1 (human) ( 36 ) , DDX5 (human) ( 45 ) , DKK1 (human) ( 29 ) , GLIPR1 (human) ( 26 ) , GSKIP (human) ( 12 ) , IL24 (human) ( 16 ) , Merlin (human) ( 15 ) , PPP2R2A (human) ( 14 ) , SFRP2 (human) ( 32 ) , WNT3A (human) ( 10 , 25 ) , WNT5A (human) ( 37 )
Putative in vivo kinases:
GSK3B (human) ( 10 , 57 ) , IKKA (human) ( 52 ) , JNK1 (human) ( 35 )
Kinases, in vitro:
GSK3A (human) ( 57 ) , GSK3B (human) ( 5 , 39 , 48 , 56 ) , JNK1 (human) ( 35 )
Phosphatases, in vitro:
PPP2CA (human) ( 39 )
Treatments:
anti-FGF19 ( 40 ) , calyculin_A ( 31 ) , cAMP_analog ( 48 ) , CHIR99021 ( 6 ) , CK1-7 ( 56 ) , colforsin ( 47 ) , CTGF ( 29 ) , FGF2 ( 25 ) , H-89 ( 56 ) , KY1022 ( 11 ) , lithium ( 31 , 54 , 56 , 57 ) , LY2090314 ( 20 ) , MG132 ( 12 , 40 , 54 ) , okadaic_acid ( 35 ) , olaparib ( 4 ) , SB216763 ( 43 ) , SB415286 ( 6 ) , SP600125 ( 35 ) , Wnt ( 57 ) , Wnt3a ( 33 , 56 )

Downstream Regulation
Effects of modification on CTNNB1:
activity, inhibited ( 44 ) , intracellular localization ( 34 , 38 , 41 , 45 ) , molecular association, regulation ( 35 ) , protein degradation ( 4 , 5 , 26 , 38 , 39 , 56 ) , ubiquitination ( 49 )
Effects of modification on biological processes:
cell adhesion, altered ( 35 ) , cell growth, altered ( 38 , 55 ) , cytoskeletal reorganization ( 33 ) , signaling pathway regulation ( 4 , 5 ) , transcription, altered ( 38 , 44 ) , transcription, inhibited ( 5 , 24 , 26 , 58 )
Induce interaction with:
CBLL1 (mouse) ( 35 )

Disease / Diagnostics Relevance
Relevant diseases:
colorectal cancer ( 57 ) , ovarian cancer ( 46 ) , melanoma skin cancer ( 46 )

References 

1

Kim DK, et al. (2021) TRIB2 Stimulates Cancer Stem-Like Properties through Activating the AKT-GSK3β-β-Catenin Signaling Axis. Mol Cells 44, 481-492
34326276   Curated Info

2

Wang J, et al. (2021) Enhancement of E-cadherin expression and processing and driving of cancer cell metastasis by ARID1A deficiency. Oncogene
34290402   Curated Info

3

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

4

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

5

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

6

Jungers CF, et al. (2020) Regulation of eukaryotic translation initiation factor 6 dynamics through multisite phosphorylation by GSK3. J Biol Chem
32703900   Curated Info

7

Aros CJ, et al. (2020) High-Throughput Drug Screening Identifies a Potent Wnt Inhibitor that Promotes Airway Basal Stem Cell Homeostasis. Cell Rep
32075752   Curated Info

8

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

9

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

10

Lee SK, et al. (2018) β-Catenin-RAS interaction serves as a molecular switch for RAS degradation via GSK3β. EMBO Rep 19
30413483   Curated Info

11

Cho YH, et al. (2016) KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer. Oncotarget 7, 81727-81740
27835580   Curated Info

12

Dema A, et al. (2016) The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3β Interaction Protein (GSKIP) Regulates β-Catenin through Its Interactions with Both Protein Kinase A (PKA) and GSK3β. J Biol Chem 291, 19618-30
27484798   Curated Info

13

Li CC, et al. (2016) Enhancement of β-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals. Proc Natl Acad Sci U S A 113, 5946-51
27162341   Curated Info

14

Hein AL, et al. (2016) PR55α Subunit of Protein Phosphatase 2A Supports the Tumorigenic and Metastatic Potential of Pancreatic Cancer Cells by Sustaining Hyperactive Oncogenic Signaling. Cancer Res 76, 2243-53
26893480   Curated Info

15

Morrow KA, et al. (2016) Loss of tumor suppressor Merlin results in aberrant activation of Wnt/β-catenin signaling in cancer. Oncotarget 7, 17991-8005
26908451   Curated Info

16

Panneerselvam J, et al. (2015) Phosphorylation of interleukin (IL)-24 is required for mediating its anti-cancer activity. Oncotarget 6, 16271-86
26009991   Curated Info

17

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

18

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

19

Xue J, et al. (2015) Tumour suppressor TRIM33 targets nuclear β-catenin degradation. Nat Commun 6, 6156
25639486   Curated Info

20

Atkinson JM, et al. (2015) Activating the Wnt/β-Catenin Pathway for the Treatment of Melanoma--Application of LY2090314, a Novel Selective Inhibitor of Glycogen Synthase Kinase-3. PLoS One 10, e0125028
25915038   Curated Info

21

Zarling AL, et al. (2014) MHC-restricted phosphopeptides from insulin receptor substrate-2 and CDC25b offer broad-based immunotherapeutic agents for cancer. Cancer Res 74, 6784-95
25297629   Curated Info

22

Choi SH, et al. (2013) α-Catenin interacts with APC to regulate β-catenin proteolysis and transcriptional repression of Wnt target genes. Genes Dev 27, 2473-88
24240237   Curated Info

23

Schofield AV, Gamell C, Bernard O (2013) Tubulin polymerization promoting protein 1 (TPPP1) increases β-catenin expression through inhibition of HDAC6 activity in U2OS osteosarcoma cells. Biochem Biophys Res Commun 436, 571-7
23727580   Curated Info

24

Imajo M, et al. (2012) A molecular mechanism that links Hippo signalling to the inhibition of Wnt/β-catenin signalling. EMBO J 31, 1109-22
22234184   Curated Info

25

Krejci P, et al. (2012) Receptor Tyrosine Kinases Activate Canonical WNT/β-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct β-Catenin Phosphorylation. PLoS One 7, e35826
22558232   Curated Info

26

Li L, et al. (2011) GLIPR1 suppresses prostate cancer development through targeted oncoprotein destruction. Cancer Res 71, 7694-704
22025562   Curated Info

27

Moritz A (2011) CST Curation Set: 12371; Year: 2011; Biosample/Treatment: cell line, MKN-45/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

28

Omori E, Matsumoto K, Ninomiya-Tsuji J (2011) Non-canonical β-catenin degradation mediates reactive oxygen species-induced epidermal cell death. Oncogene 30, 3336-44
21383695   Curated Info

29

Rooney B, et al. (2011) CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: implications for the pathogenesis of diabetic nephropathy. FEBS Lett 585, 531-8
21237163   Curated Info

30

Rikova K (2011) CST Curation Set: 10911; Year: 2011; Biosample/Treatment: cell line, NCI-H520/untreated; Disease: non-small cell squamous cell lung carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

31

Kwon IK, et al. (2010) PKG inhibits TCF signaling in colon cancer cells by blocking beta-catenin expression and activating FOXO4. Oncogene 29, 3423-34
20348951   Curated Info

32

Yamamura S, et al. (2010) Oncogenic functions of secreted Frizzled-related protein 2 in human renal cancer. Mol Cancer Ther 9, 1680-7
20501806   Curated Info

33

Hadjihannas MV, Brückner M, Behrens J (2010) Conductin/axin2 and Wnt signalling regulates centrosome cohesion. EMBO Rep 11, 317-24
20300119   Curated Info

34

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

35

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

36

Wu H, Symes K, Seldin DC, Dominguez I (2009) Threonine 393 of beta-catenin regulates interaction with Axin. J Cell Biochem 108, 52-63
19565571   Curated Info

37

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

38

Dar AA, Belkhiri A, El-Rifai W (2009) The aurora kinase A regulates GSK-3beta in gastric cancer cells. Oncogene 28, 866-75
19060929   Curated Info

39

Su Y, et al. (2008) APC is essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase. Mol Cell 32, 652-61
19061640   Curated Info

40

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

41

Li FQ, Mofunanya A, Harris K, Takemaru K (2008) Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity. J Cell Biol 181, 1141-54
18573912   Curated Info

42

Huang P, Senga T, Hamaguchi M (2007) A novel role of phospho-beta-catenin in microtubule regrowth at centrosome. Oncogene 26, 4357-71
17260019   Curated Info

43

Coluccia AM, et al. (2007) Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation. EMBO J 26, 1456-66
17318191   Curated Info

44

Wu B, Crampton SP, Hughes CC (2007) Wnt signaling induces matrix metalloproteinase expression and regulates T cell transmigration. Immunity 26, 227-39
17306568   Curated Info

45

Yang L, Lin C, Liu ZR (2006) P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin. Cell 127, 139-55
17018282   Curated Info

46

Zarling AL, et al. (2006) Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy. Proc Natl Acad Sci U S A 103, 14889-94
17001009   Curated Info

47

Taurin S, et al. (2006) Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase. J Biol Chem 281, 9971-6
16476742   Curated Info

48

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

49

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

50

Chan SM, et al. (2004) Protein microarrays for multiplex analysis of signal transduction pathways. Nat Med 10, 1390-6
15558056   Curated Info

51

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

52

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

53

Kim HS, et al. (2002) Regulation of angiogenesis by glycogen synthase kinase-3beta. J Biol Chem 277, 41888-96
12167628   Curated Info

54

Sadot E, et al. (2002) Regulation of S33/S37 phosphorylated beta-catenin in normal and transformed cells. J Cell Sci 115, 2771-80
12077367   Curated Info

55

van Noort M, van de Wetering M, Clevers H (2002) Identification of two novel regulated serines in the N terminus of beta-catenin. Exp Cell Res 276, 264-72
12027456   Curated Info

56

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

57

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

58

Staal FJ, Noort Mv M, Strous GJ, Clevers HC (2002) Wnt signals are transmitted through N-terminally dephosphorylated beta-catenin. EMBO Rep 3, 63-8
11751573   Curated Info

59

Winston JT, et al. (1999) The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes Dev 13, 270-83
9990852   Curated Info

60

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