Ser37
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Home > Phosphorylation Site Page: > Ser37  -  CTNNB1 (human)

Site Information
yLDsGIHsGATtTAP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447582

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 50 ) , immunoprecipitation ( 3 , 4 , 9 , 15 , 35 , 37 , 38 ) , mass spectrometry ( 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 32 , 40 , 55 ) , mass spectrometry (in vitro) ( 35 ) , mutation of modification site ( 6 , 9 , 15 , 36 , 41 , 42 , 46 , 49 , 50 , 52 , 53 , 54 , 55 , 57 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 9 , 11 , 16 , 28 , 30 , 31 , 33 , 34 , 35 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 9 , 11 , 15 , 16 , 28 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 44 , 48 , 49 , 51 , 52 , 53 , 55 , 56 , 57 )
Disease tissue studied:
bone cancer ( 33 ) , breast cancer ( 6 , 37 , 53 ) , colorectal cancer ( 1 , 15 , 30 , 34 , 39 , 40 , 49 , 52 ) , colorectal carcinoma ( 1 , 15 , 30 , 34 , 39 , 40 , 49 , 52 ) , gastric cancer ( 14 , 38 ) , gastric carcinoma ( 14 , 38 ) , kidney cancer ( 31 ) , leukemia ( 41 ) , chronic myelogenous leukemia ( 41 ) , lung cancer ( 29 , 32 ) , non-small cell lung cancer ( 29 , 32 ) , non-small cell squamous cell lung carcinoma ( 29 ) , pancreatic cancer ( 5 ) , pancreatic carcinoma ( 5 ) , prostate cancer ( 16 ) , melanoma skin cancer ( 11 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 2 , 3 , 44 , 45 , 55 ) , 293T (epithelial) ( 15 , 30 , 39 , 52 , 53 , 54 , 57 , 58 ) , 4T1 (breast cell) ( 37 ) , A375 (melanocyte) ( 11 ) , A431 (epithelial) ( 35 ) , A498 (renal) [SFRP2 (human), transfection] ( 31 ) , AGS (gastric) ( 38 ) , BC-1 (B lymphocyte) ( 41 ) , C4-2 (prostate cell) ( 16 ) , C57MG (epithelial) ( 36 ) , Caco-2 (intestinal) ( 15 ) , Capan1 (pancreatic) ( 5 ) , CD18/HPAF (pancreatic) ( 5 ) , CHO (fibroblast) ( 57 ) , COLO-320 (intestinal) ( 1 ) , COS (fibroblast) ( 44 , 50 , 53 , 54 ) , DLD1 (intestinal) ( 39 ) , endothelial-vein ( 51 ) , FTC-133 (thyroid cell) ( 47 ) , HCT116 (intestinal) ( 30 , 40 , 52 ) , HeLa (cervical) ( 3 , 4 , 55 , 58 ) , HT-29 (intestinal) ( 43 , 52 ) , HUVEC (endothelial) ( 42 ) , Jurkat (T lymphocyte) ( 48 , 55 ) , KU812 (myeloid) ( 41 ) , L cells (fibroblast) ( 55 ) , L3.6p1 (pancreatic) ( 5 ) , Ls174T (intestinal) ( 49 ) , lung ( 32 ) , MCF-7 (breast cell) ( 6 , 37 ) , MDCK (epithelial) ( 46 , 52 ) , MEF (fibroblast) [axin 2 (mouse), homozygous knockout] ( 33 ) , mesangial ( 28 ) , MKN-45 (gastric) ( 14 ) , MKN-74 (gastric) ( 38 ) , NCI-H520 (squamous) ( 29 ) , oocyte ( 56 ) , Rat2 (fibroblast) ( 56 ) , SKBr3 (breast cell) ( 53 ) , SNU16Ad (gastric) ( 38 ) , SUM159 (breast cell) ( 6 ) , SW480 (intestinal) ( 30 , 34 , 52 ) , SW620 (intestinal) ( 30 ) , U2OS (bone cell) ( 33 )

Upstream Regulation
Regulatory protein:
AurA (human) ( 38 ) , axin 1 (human) ( 55 ) , CDH2 (human) ( 52 ) , CTNNB1 (human) ( 36 ) , DDX5 (human) ( 43 ) , DKK1 (human) ( 28 ) , GSKIP (human) ( 3 ) , Merlin (human) ( 6 ) , PPP2R2A (human) ( 5 ) , SFRP2 (human) ( 31 ) , WNT5A (human) ( 37 )
Putative in vivo kinases:
GSK3B (human) ( 56 ) , IKKA (human) ( 50 ) , JNK1 (human) ( 35 )
Kinases, in vitro:
GSK3A (human) ( 56 ) , GSK3B (human) ( 39 , 45 , 55 ) , JNK1 (human) ( 35 )
Phosphatases, in vitro:
PPP2CA (human) ( 39 )
Treatments:
anti-FGF19 ( 40 ) , calyculin_A ( 30 ) , cAMP_analog ( 45 ) , CK1-7 ( 55 ) , colforsin ( 44 ) , CTGF ( 28 ) , H-89 ( 55 ) , IWR-1 ( 1 ) , KN-92 ( 47 ) , KN-93 ( 47 ) , KY1022 ( 2 ) , lithium ( 30 , 52 , 54 , 55 , 56 , 57 ) , LLnL ( 54 , 57 ) , LY2090314 ( 11 ) , MG132 ( 3 , 40 , 52 ) , okadaic_acid ( 35 ) , SB216763 ( 41 ) , SP600125 ( 35 ) , W-5 ( 47 ) , W-7 ( 47 ) , Wnt ( 54 , 56 , 57 ) , Wnt3a ( 33 )

Downstream Regulation
Effects of modification on CTNNB1:
intracellular localization ( 34 , 38 , 43 ) , molecular association, regulation ( 35 ) , protein degradation ( 6 , 38 , 39 , 42 , 55 ) , ubiquitination ( 46 )
Effects of modification on biological processes:
cell adhesion, altered ( 35 ) , cell growth, altered ( 38 , 53 ) , cytoskeletal reorganization ( 33 ) , transcription, altered ( 38 , 42 ) , transcription, inhibited ( 15 )
Induce interaction with:
CBLL1 (mouse) ( 35 )

Disease / Diagnostics Relevance
Relevant diseases:
colorectal cancer ( 56 )

References 

1

Mashima T, et al. (2017) mTOR signaling mediates resistance to tankyrase inhibitors in Wnt-driven colorectal cancer. Oncotarget 8, 47902-47915
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2

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

3

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
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4

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
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5

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

6

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

7

Panneerselvam J, et al. (2015) Phosphorylation of interleukin (IL)-24 is required for mediating its anti-cancer activity. Oncotarget 6, 16271-86
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8

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
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9

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
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10

Xue J, et al. (2015) Tumour suppressor TRIM33 targets nuclear β-catenin degradation. Nat Commun 6, 6156
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11

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
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12

Vinyoles M, et al. (2014) Multivesicular GSK3 sequestration upon Wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6. Mol Cell 53, 444-57
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13

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
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14

Zhou J (2012) CST Curation Set: 14009; Year: 2012; Biosample/Treatment: cell line, MKN-45/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine (P-Tyr-1000) Rabbit mAb Cat#: 8954, Phospho-Tyrosine Rabbit mAb (p-Tyr-1000) Immunoaffinity Beads Cat#: 8876
Curated Info

15

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
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16

Du C, et al. (2012) Beta-catenin phosphorylated at threonine 120 antagonizes generation of active beta-catenin by spatial localization in trans-Golgi network. PLoS One 7, e33830
22511927   Curated Info

17

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
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18

Li L, et al. (2011) GLIPR1 suppresses prostate cancer development through targeted oncoprotein destruction. Cancer Res 71, 7694-704
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19

Rikova K (2011) CST Curation Set: 13113; Year: 2011; Biosample/Treatment: cell line, MGH-1/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

20

Rikova K (2011) CST Curation Set: 13114; Year: 2011; Biosample/Treatment: cell line, MGH-2/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

21

Rikova K (2011) CST Curation Set: 13115; Year: 2011; Biosample/Treatment: cell line, MGH-3/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

22

Rikova K (2011) CST Curation Set: 13116; Year: 2011; Biosample/Treatment: cell line, MGH-4/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

23

Rikova K (2011) CST Curation Set: 13117; Year: 2011; Biosample/Treatment: cell line, MGH-5/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

24

Rikova K (2011) CST Curation Set: 13118; Year: 2011; Biosample/Treatment: cell line, MGH-6/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

25

Rikova K (2011) CST Curation Set: 13119; Year: 2011; Biosample/Treatment: cell line, MGH-7/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

26

Rikova K (2011) CST Curation Set: 13121; Year: 2011; Biosample/Treatment: cell line, MGH-9/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

27

Rikova K (2011) CST Curation Set: 13122; Year: 2011; Biosample/Treatment: cell line, MGH-10/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

28

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
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29

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

30

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

31

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

32

Rikova K (2010) CST Curation Set: 9757; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
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
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35

Lee MH, Koria P, Qu J, Andreadis ST (2009) JNK phosphorylates beta-catenin and regulates adherens junctions. FASEB J 23, 3874-83
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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
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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
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38

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

Coluccia AM, et al. (2007) Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation. EMBO J 26, 1456-66
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42

Leung KW, Pon YL, Wong RN, Wong AS (2006) Ginsenoside-Rg1 induces vascular endothelial growth factor expression through the glucocorticoid receptor-related phosphatidylinositol 3-kinase/Akt and beta-catenin/T-cell factor-dependent pathway in human endothelial cells. J Biol Chem 281, 36280-8
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43

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
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44

Taurin S, et al. (2006) Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase. J Biol Chem 281, 9971-6
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45

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
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46

Provost E, et al. (2005) Functional correlates of mutation of the Asp32 and Gly34 residues of beta-catenin. Oncogene 24, 2667-76
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47

Kremenevskaja N, et al. (2005) Wnt-5a has tumor suppressor activity in thyroid carcinoma. Oncogene 24, 2144-54
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48

Chan SM, et al. (2004) Protein microarrays for multiplex analysis of signal transduction pathways. Nat Med 10, 1390-6
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49

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
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50

Provost E, et al. (2003) Functional correlates of mutations in beta-catenin exon 3 phosphorylation sites. J Biol Chem 278, 31781-9
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51

Kim HS, et al. (2002) Regulation of angiogenesis by glycogen synthase kinase-3beta. J Biol Chem 277, 41888-96
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52

Sadot E, et al. (2002) Regulation of S33/S37 phosphorylated beta-catenin in normal and transformed cells. J Cell Sci 115, 2771-80
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53

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
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54

van Noort M, et al. (2002) Wnt signaling controls the phosphorylation status of beta-catenin. J Biol Chem 277, 17901-5
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55

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
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56

Liu C, et al. (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108, 837-47
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57

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58

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59

Orford K, et al. (1997) Serine phosphorylation-regulated ubiquitination and degradation of beta-catenin. J Biol Chem 272, 24735-8
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