Stimulation of the WNT pathway results in the recruitment of...

created [InstanceEdit:3640817] Rothfels, K, 2013-05-29
dbId 3640818
displayName Stimulation of the WNT pathway results in the recruitment of...
modified [InstanceEdit:5333076] Rothfels, K, 2014-02-18
schemaClass Summation
text Stimulation of the WNT pathway results in the recruitment of the GSK3beta:AXIN complex to the membrane (Willert et al, 1999; Schwarz Romond et al, 2007; Bilic et al, 2007; reviewed in Saito-Diaz et al, 2013). Activation of WNT signaling is believed to transiently inhibit GSK3beta kinase activity preventing its phosphorylation of beta-catenin (described in detail in the pathway "Degradation of beta-catenin by the destruction complex"; Piao et al, 2008; reviewed in Saito-Diaz et al, 2013). Inhibition of GSK3beta activity also prevents phosphorylation of AXIN allowing the constitutive dephosphorylation of AXIN at GSK3beta-dependent phosphorylation sites by PP2A predominate. This is believed to weaken the interaction between AXIN and beta-catenin (Willert et al, 1999). AXIN has also been shown to be dephosphorylated by PP1 at several serinve residues initially phosphorylated by CSNK1. The dephosphorylation by PP1 weakens the interaction between AXIN-GSK3beta and inhibits beta-catenin phosphorylation/degradation (Luo et al, 2007; reviewed in Huang et al, 2008). A recent study suggests that sustained inactivation of GSK3beta may result from its sequestration in multivesicular bodies (Taelman et al, 2010; reviewed in Niehrs and Acebon, 2010; Schuldt, 2011). Together, these changes destabilize the destruction complex and allow beta-catenin to accumulate.
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