Catenin (cadherin-associated protein), beta 1, 88kDa
|PDB rendering based on 1dow.|
|RNA expression pattern|
Beta-catenin is a subunit of the cadherin protein complex. In Drosophila, the homologous protein is called armadillo. Beta-catenin has been implicated as an integral component in the Wnt signaling pathway.
When beta-catenin was sequenced it was found to be a member of the armadillo family of proteins. These proteins have multiple copies of the so-called armadillo repeat domain which is specialized for protein-protein binding. An increase in beta-catenin production has been noted in those people who have Basal Cell Carcinoma and leads to the increase in proliferation of related tumors. When beta-catenin is not associated with cadherins and alpha-catenin, it can interact with other proteins such as ICAT and APC.
Role in Liver Biology
Recent evidence suggests that beta-catenin plays an important role in various aspects of liver biology including liver development (both embryonic and postnatal), liver regeneration following partial hepatectomy. HGF-induced hepatpomegaly, liver zonation, and pathogenesis of liver cancer.
Interactions of beta-catenin with other proteins
As mentioned above, beta-catenin contains armadillo repeats and is able to bind to other proteins. Inside cells, beta-catenin can be found in complexes with cadherins, transcription factors (TF in Figure 2) and other proteins such as axin, a component of the Wnt signalling pathway. The ability of beta-catenin to bind to other proteins is regulated by tyrosine kinases and serine kinases such as GSK-3.
When beta-catenin is not assembled in complexes with cadherins, it can form a complex with axin. While bound to axin, beta-catenin can be phosphorylated by GSK-3, which creates a signal for the rapid ubiquitin-dependent degradation of beta-catenin by proteosomes. Various signals such as the Wnt signalling pathway can inhibit GSK-3-mediated phosphorylation of beta-catenin, allowing beta-catenin to go to the cell nucleus, interact with transcription factors, and regulate gene transcription.
Beta-catenin can be phosphorylated by other kinases such as protein kinase A (PKA). Phosphorylation of beta-catenin by PKA has been associated with reduced degradation of beta-catenin, increased levels of beta-catenin in the nucleus and interaction of beta-catenin with TCF family transcription factors to regulate gene expression.
The Role of Beta-Catenin in The Wnt Signaling Pathway
When Wnt is not present, GSK3 (a kinase) constitutively phosphorylates the beta-catenin protein. Beta-catenin is associated with Axin (scaffolding protein) complexed with GSK3 and APC (adenomatosis polyposis coli). The creation of said complex acts to substantially increase the phosphorylation of beta-catenin by facilitating the the action of GSK3. When beta-catenin is phosphorylated it is degraded and thus will not build up in the cell to a significant level. When Wnt binds to Frizzled (Fz), its receptor, dishevelled (Dsh) is recruited to the membrane. GSK3 is inhibited by the activation of Dsh by Fz. Because of this, beta-catenin is permited to build up in the cytosol and can be subsequently translocated into the nucleus to perform a variety of functions. It can act in conjunction with TCF to activate specific genes as well as cause the export of TCF from the nucleus.
- MeSH Beta+Catenin
- "A diverse set of proteins modulate the canonical Wnt/beta-catenin signaling pathway." at cancer.gov
- "The role of beta-catenin in signal transduction, cell fate determination and trans-differentiation" at nih.gov
- ↑ G. Saldanha, V. Ghura, L. Potter and A. Fletcher. "Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation" in The British Journal of Dermatology (2004) Volume 151, pages 157-164. Entrez PubMed 15270885
- ↑ Thompson MD, Monga SP (2007). "WNT/beta-catenin signaling in liver health and disease". Hepatology 45 (5): 1298-305. doi:10.1002/hep.21651. PMID 17464972.
- ↑ J. Lilien and J. Balsamo "The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin" in Current opinion in cell biology (2005) Volume 17, pages 459-465. Entrez PubMed 16099633
- ↑ M. D. Castellone, H. Teramoto, B. O. Williams, K. M. Druey, J. S. Gutkind. "Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis" in Science (2005) Volume 310, pages 1504-1510. Entrez PubMed 16293724
- ↑ X. Liu, J. S. Rubin and A. R. Kimmel. "Rapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin stabilization are mediated by Galpha proteins" in Current Biology (2005) Volume 15, pages 1989-1997. Entrez PubMed 16303557
- ↑ S. Hino, C. Tanji, K. I. Nakayama and A. Kikuchi "Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination" in Molecular and Cellular Biology (2005) Volume 20, pages 9063-9072. Entrez PubMed 16199882
- Kikuchi A (2000). "Regulation of beta-catenin signaling in the Wnt pathway.". Biochem. Biophys. Res. Commun. 268 (2): 243-8. doi:10.1006/bbrc.1999.1860. PMID 10679188.
- Wilson PD (2001). "Polycystin: new aspects of structure, function, and regulation.". J. Am. Soc. Nephrol. 12 (4): 834-45. PMID 11274246.
- Kalluri R, Neilson EG (2004). "Epithelial-mesenchymal transition and its implications for fibrosis.". J. Clin. Invest. 112 (12): 1776-84. doi:10.1172/JCI200320530. PMID 14679171.
- De Ferrari GV, Moon RT (2007). "The ups and downs of Wnt signaling in prevalent neurological disorders.". Oncogene 25 (57): 7545-53. doi:10.1038/sj.onc.1210064. PMID 17143299.
Proteins of the cytoskeleton
|Microfilaments||Actins - Actin-binding proteins - Actinin - Arp2/3 complex - Cofilin - Destrin - Gelsolin - Myosins - Profilin - Tropomodulin - Troponin (T, C, I) - Tropomyosin - Wiskott-Aldrich syndrome protein|
|Intermediate filaments||type 1 and 2 (Cytokeratin, type I, type II) - type 3 (Desmin, GFAP, Peripherin, Vimentin) - type 4 (Internexin, Nestin, Neurofilament, Synemin, Syncoilin) - type 5 (Lamin A, B)|
|Microtubules||Dyneins - Kinesins - MAPs (Tau protein, Dynamin) - Tubulins - Stathmin - Tektin|
|Catenins||Alpha catenin - Beta catenin - Plakoglobin (gamma catenin) - Delta catenin|
|Nonhuman||Major sperm proteins - Prokaryotic cytoskeleton (Crescentin, FtsZ, MreB)|
|Other||APC - Dystrophin (Dystroglycan) - plakin (Desmoplakin, Plectin) - Spectrin - Talin - Utrophin - Vinculin|
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