Anti-Phospho-β-Catenin: Rabbit Beta-Catenin, Phospho-Thr41/Ser45, Antibody

BACKGROUND The protein beta-Catenin was first described in humans as a member of the cell membrane-bound adherens complex.  A second role for beta-Catenin in cell-signaling was discovered, which involves translocation of this protein from the cytoplasm into the nucleus. beta-Catenin may be regarded as existing in three different subcellular forms: membrane-bound (as part of the adherens complex), cytosolic, and nuclear. Binding of the protein to other members of the adherens complex, ie, E-cadherin and alpha-Catenin, is thought to be regulated by tyrosine phosphorylation. Tyrosine phosphorylation of beta-Catenin leads to its dissociation from the adherens complex to the cytosol.¹ Cytosolic beta-Catenin may subsequently be translocated into the nucleus or be degraded. In nucleus, beta-Catenin binds with a member of the TCF/LEF family of transcription factors to form a complex that activates transcription of target genes by binding to their promoter sequences.² The degradation of beta-Catenin involves binding of the protein to a complex involving APC protein, and two further proteins, AXIN and glycogen synthase kinase (GSK)-3beta. The latter serves to phosphorylate serine and threonine residues on beta-Catenin (Thr41, Ser37 and Ser33), a crucial step required to target the protein for ubiquitination and proteosomal degradation. Both APC and AXIN enhance this phosphorylation. Moreover, CK1 phosphorylates Ser45 of beta-Catenin generating a priming site for the subsequent phosphorylation by GSK-3beta.   Phosphorylation of beta-Catenin is important in enabling binding to the F box protein beta-TrCP and hence ubiquitin-mediated proteolysis.³ Wnt signaling pathway plays important role in regulation of this process.⁴ Binding of Wnt family glycoproteins to their trans-membrane receptor, Frz, leads to increased activity of the protein Dishevelled (Dvl) that, in turn, inhibits GSK-3beta phosphorylating activity, which leads to increase of cytosolic beta-Catenin and its nuclear translocation. However, it has recently been shown that beta-Catenin may also be targeted for such degradation independent of GSK-3beta-mediated phosphorylation. This putative alternative pathway requires interaction between beta-Catenin, APC, and a complex of proteins including the p53-inducible protein, Siah-1.⁵

 

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