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 ( 33 ) , immunoprecipitation ( 2 , 3 , 8 , 20 , 22 , 23 ) , mass spectrometry ( 24 , 36 ) , mass spectrometry (in vitro) ( 20 ) , mutation of modification site ( 5 , 8 , 21 , 26 , 30 , 32 , 33 , 35 , 36 , 38 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 8 , 10 , 12 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 8 , 10 , 12 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 31 , 32 , 34 , 36 , 37 , 38 )
Disease tissue studied:
bone cancer ( 18 ) , breast cancer ( 5 , 22 , 25 ) , colorectal cancer ( 1 , 16 , 19 , 24 , 32 ) , colorectal carcinoma ( 1 , 16 , 19 , 24 , 32 ) , gastric cancer ( 23 ) , gastric carcinoma ( 23 ) , kidney cancer ( 17 ) , leukemia ( 26 ) , chronic myelogenous leukemia ( 26 ) , pancreatic cancer ( 4 ) , pancreatic carcinoma ( 4 ) , prostate cancer ( 12 ) , melanoma skin cancer ( 10 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 2 , 28 , 29 , 36 ) , 293T (epithelial) ( 16 , 35 , 38 ) , 4T1 (breast cell) ( 22 ) , A375 (melanocyte) ( 10 ) , A431 (epithelial) ( 20 ) , A498 (renal) [SFRP2 (human), transfection] ( 17 ) , AGS (gastric) ( 23 ) , BC-1 (B lymphocyte) ( 26 ) , C4-2 (prostate cell) ( 12 ) , C57MG (epithelial) ( 21 ) , Capan1 (pancreatic) ( 4 ) , CD18/HPAF (pancreatic) ( 4 ) , CHO (fibroblast) ( 38 ) , COLO-320 (intestinal) ( 1 ) , COS (fibroblast) ( 28 , 33 , 35 ) , endothelial-vein ( 34 ) , HCT116 (intestinal) ( 16 , 24 ) , HeLa (cervical) ( 2 , 3 , 36 ) , HT-29 (intestinal) ( 27 ) , Jurkat (T lymphocyte) ( 31 , 36 ) , KU812 (myeloid) ( 26 ) , L cells (fibroblast) ( 36 ) , L3.6p1 (pancreatic) ( 4 ) , Ls174T (intestinal) ( 32 ) , MCF-7 (breast cell) ( 5 , 22 , 25 ) , MDCK (epithelial) ( 30 ) , MEF (fibroblast) [axin 2 (mouse), homozygous knockout] ( 18 ) , MKN-74 (gastric) ( 23 ) , oocyte ( 37 ) , Rat2 (fibroblast) ( 37 ) , SNU16Ad (gastric) ( 23 ) , SUM159 (breast cell) ( 5 ) , SW480 (intestinal) ( 16 , 19 ) , SW620 (intestinal) ( 16 ) , U2OS (bone cell) ( 18 )

Upstream Regulation
Regulatory protein:
AurA (human) ( 23 ) , axin 1 (human) ( 36 ) , CTNNB1 (human) ( 21 ) , DDX5 (human) ( 27 ) , GSKIP (human) ( 2 ) , JNK1 (human) ( 20 ) , JNK2 (human) ( 20 ) , Merlin (human) ( 5 ) , PPP2R2A (human) ( 4 ) , SFRP2 (human) ( 17 ) , SMPD3 (human) ( 25 ) , WNT5A (human) ( 22 )
Putative in vivo kinases:
GSK3B (human) ( 37 ) , IKKA (human) ( 33 ) , JNK1 (human) ( 20 )
Kinases, in vitro:
GSK3A (human) ( 37 ) , GSK3B (human) ( 29 , 36 ) , JNK1 (human) ( 20 )
Putative upstream phosphatases:
PPP1CC (human) ( 25 )
Treatments:
anti-FGF19 ( 24 ) , C6-ceramide ( 25 ) , calyculin_A ( 16 , 25 ) , cAMP_analog ( 29 ) , CK1-7 ( 36 ) , colforsin ( 28 ) , H-89 ( 36 ) , high_cell_density ( 25 ) , IWR-1 ( 1 ) , lithium ( 16 , 35 , 36 , 37 , 38 ) , LLnL ( 35 , 38 ) , LY2090314 ( 10 ) , MG132 ( 2 , 24 ) , okadaic_acid ( 20 , 25 ) , SB216763 ( 26 ) , siRNA ( 25 ) , SP600125 ( 20 ) , Wnt ( 35 , 37 , 38 ) , Wnt3a ( 18 , 36 )

Downstream Regulation
Effects of modification on CTNNB1:
intracellular localization ( 19 , 23 , 27 ) , molecular association, regulation ( 19 , 20 ) , protein degradation ( 23 , 36 )
Effects of modification on biological processes:
cell adhesion, altered ( 20 ) , cell growth, altered ( 23 ) , cytoskeletal reorganization ( 18 ) , transcription, altered ( 23 )
Induce interaction with:
CBLL1 (human) ( 19 ) , CBLL1 (mouse) ( 20 )

Disease / Diagnostics Relevance
Relevant diseases:
colorectal cancer ( 37 )

References 

1

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

2

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

3

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

4

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

5

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

6

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

7

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

8

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

9

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

10

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

11

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

12

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

13

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

14

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

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

17

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

18

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

19

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

20

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

21

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

22

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

23

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

24

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

25

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

26

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

27

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

28

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

29

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

30

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

31

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

32

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

33

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

34

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

35

van Noort M, et al. (2002) Wnt signaling controls the phosphorylation status of beta-catenin. J Biol Chem 277, 17901-5
11834740   Curated Info

36

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

37

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

38

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