Dear all,
I think I have been thinking too much about this. Can someone clarify please - just to make sure I am getting it right.
1. GSK3B phosphorylation at Ser9 will decrease GSK3B activity
2. Reduction of GSK3B activity will decrease B-Catenin degradation
3. This is compatible with an increase in canonical WNT activity - e.i. this could have been caused by an increase in canonical WNT activity.
Thanks!
Sounds legit. S9 phosphorylation in GSK3β causes N-terminal tail to act as pseudosubstrate, hindering binding of the actual substrates, thus inhibiting GSK3 activity and causing beta-catenin accumulation.
Activation of Wnt signaling disrupts the complex of complex of Axin, APC), CK1, GSK3β and β-catenin, blocking phosphorylation of β-catenin by GSK3, resulting in β-catenin stabilization - same outcome as S9 phosphorylation.