Thr41
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Home > Phosphorylation Site Page: > Thr41  -  CTNNB1 (human)

Site Information
GIHsGATtTAPsLsG   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447583

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 43 ) , immunoassay ( 25 ) , immunoprecipitation ( 12 , 13 , 18 , 30 , 32 , 33 ) , mass spectrometry ( 34 , 46 ) , mass spectrometry (in vitro) ( 30 ) , mutation of modification site ( 10 , 15 , 18 , 31 , 36 , 40 , 42 , 43 , 45 , 46 , 48 ) , phospho-antibody ( 4 , 5 , 6 , 11 , 12 , 13 , 14 , 15 , 18 , 20 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 44 , 45 , 46 , 47 , 48 ) , western blotting ( 4 , 5 , 6 , 11 , 12 , 13 , 14 , 15 , 18 , 20 , 22 , 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 38 , 41 , 42 , 44 , 46 , 47 , 48 )
Disease tissue studied:
bone cancer ( 28 ) , breast cancer ( 4 , 15 , 32 , 35 ) , breast ductal carcinoma ( 4 ) , breast cancer, triple negative ( 4 ) , chondrosarcoma ( 23 ) , colorectal cancer ( 6 , 11 , 26 , 29 , 34 , 42 ) , colorectal carcinoma ( 6 , 11 , 26 , 29 , 34 , 42 ) , gastric cancer ( 33 ) , gastric carcinoma ( 33 ) , kidney cancer ( 27 ) , leukemia ( 36 ) , chronic myelogenous leukemia ( 36 ) , pancreatic cancer ( 14 ) , pancreatic carcinoma ( 14 ) , prostate cancer ( 22 , 24 ) , melanoma skin cancer ( 20 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
AurA (human) ( 33 ) , axin 1 (human) ( 5 , 46 ) , CTNNB1 (human) ( 31 ) , DDX5 (human) ( 37 ) , GLIPR1 (human) ( 24 ) , GSKIP (human) ( 12 ) , IL24 (human) ( 16 ) , JNK1 (human) ( 30 ) , JNK2 (human) ( 30 ) , Merlin (human) ( 15 ) , PPP2R2A (human) ( 14 ) , SFRP2 (human) ( 27 ) , SMPD3 (human) ( 35 ) , WNT3A (human) ( 23 ) , WNT5A (human) ( 32 )
Putative in vivo kinases:
GSK3B (human) ( 47 ) , IKKA (human) ( 43 ) , JNK1 (human) ( 30 )
Kinases, in vitro:
GSK3A (human) ( 47 ) , GSK3B (human) ( 5 , 39 , 46 ) , JNK1 (human) ( 30 )
Putative upstream phosphatases:
PPP1CC (human) ( 35 )
Treatments:
anti-FGF19 ( 34 ) , C6-ceramide ( 35 ) , calyculin_A ( 26 , 35 ) , cAMP_analog ( 39 ) , CHIR99021 ( 6 ) , CK1-7 ( 46 ) , colforsin ( 38 ) , FGF2 ( 23 ) , H-89 ( 46 ) , high_cell_density ( 35 ) , IWR-1 ( 11 ) , lithium ( 26 , 45 , 46 , 47 , 48 ) , LLnL ( 45 , 48 ) , LY2090314 ( 20 ) , MG132 ( 12 , 34 ) , okadaic_acid ( 30 , 35 ) , olaparib ( 4 ) , SB216763 ( 36 ) , SB415286 ( 6 ) , siRNA ( 35 ) , SP600125 ( 30 ) , Wnt ( 45 , 47 , 48 ) , Wnt3a ( 28 , 46 )

Downstream Regulation
Effects of modification on CTNNB1:
intracellular localization ( 29 , 33 , 37 ) , molecular association, regulation ( 29 , 30 ) , protein degradation ( 4 , 5 , 24 , 33 , 46 )
Effects of modification on biological processes:
cell adhesion, altered ( 30 ) , cell growth, altered ( 33 ) , cytoskeletal reorganization ( 28 ) , signaling pathway regulation ( 4 , 5 ) , transcription, altered ( 33 ) , transcription, inhibited ( 5 , 24 )
Induce interaction with:
CBLL1 (human) ( 29 ) , CBLL1 (mouse) ( 30 )

Disease / Diagnostics Relevance
Relevant diseases:
colorectal cancer ( 47 ) , HNSCC ( 25 )

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
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2

Wang J, et al. (2021) Enhancement of E-cadherin expression and processing and driving of cancer cell metastasis by ARID1A deficiency. Oncogene
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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
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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
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7

Aros CJ, et al. (2020) High-Throughput Drug Screening Identifies a Potent Wnt Inhibitor that Promotes Airway Basal Stem Cell Homeostasis. Cell Rep
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8

Yang W, et al. (2020) Presenilin1 exerts antiproliferative effects by repressing the Wnt/¿¿-catenin pathway in glioblastoma. Cell Commun Signal
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9

Li H, et al. (2020) Z-Ajoene Inhibits Growth of Colon Cancer by Promotion of CK1¿¿ Dependent ¿¿-Catenin Phosphorylation. Molecules
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10

Huynh H, et al. (2019) Sorafenib/MEK inhibitor combination inhibits tumor growth and the Wnt/β‑catenin pathway in xenograft models of hepatocellular carcinoma. Int J Oncol 54, 1123-1133
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11

Mashima T, et al. (2017) mTOR signaling mediates resistance to tankyrase inhibitors in Wnt-driven colorectal cancer. Oncotarget 8, 47902-47915
28615517   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
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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
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21

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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22

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

23

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

24

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

25

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

26

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

27

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

28

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

29

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

30

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

31

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

32

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

33

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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34

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

35

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

36

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

37

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

38

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

39

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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40

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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41

Chan SM, et al. (2004) Protein microarrays for multiplex analysis of signal transduction pathways. Nat Med 10, 1390-6
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42

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

43

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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44

Kim HS, et al. (2002) Regulation of angiogenesis by glycogen synthase kinase-3beta. J Biol Chem 277, 41888-96
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45

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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46

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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47

Liu C, et al. (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108, 837-47
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48

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
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