Normally in the cell, a destruction complex is assembled to regulate beta catenin levels. This complex is composed of Axin, APC( Adenomous Polypsis Coli), GSK3 beta, and CK1 alpha. Normally, on the right, the complex is assembled. CK1 alpha and GSK3 beta phosphorylate and ubiquitinate beta catenin, tagging it for proteolytic degradation facilitated by the proteosome 26S. In the presence of a WNT ligand, a 7TM receptor(abbreviated FZD) receives the signal and recruits the protein "Disheveled" to the membrane. Axin uses the disheveled protein as a docking site and stabilizes the destruction complex. Inhibitor PP2A then prevents phosphorylation and ubiquitination of beta catenin, allowing it to migrate to the nucleus. Binding to the TCF/LEF transcription factor, cell cycle progression is promoted. Alternatively, membrane bound ubiquitin ligases RNF43 and ZNRF3 downregulate the density of FZD on the cell membrane. However, a protein ligand called R - spondin is a ligand that binds LGRs 4/5/6. LGRs are also 7TM receptors. Down regulation controlled by ubiquitin ligases and up-regulation facilitated by R-spondin balances FZD concentration throughout signal transduction and cell interaction. In a tumor cell, the destruction complex fails to assemble, letting beta catenin send cell division signals automatically.
click space for next slide Tumor cells can alter the WNT pathway, which is normally responsible for facilitated cell growth.
