GSK3

GSK-3 (zw3 or shaggy in Drosophila) is a key enzyme in Wnt signaling. It phosphorylates b-catenin leading to the subsequent degradation of this molecule. The phosphorylation is primed by CK1alpha.

There are two human and mouse GSK3 genes and they are redundant (Doble 2007).

Phosphorylation of the tail of LRP is regulated by two protein kinases: GSK3 and CK1gamma (Zeng, 2005; Davidson 2005; reviewed by Nusse, 2005 .

GSK also phosphorylates the Wnt components Axin (Behrens, 1998) APC (Hart, 1998) and TCF (Lee, 2001)

GSK3 has multiple non-wnt related functions: it is involved in insulin signaling, NFAT phosphorylation and also in Hedgehog signaling (Price 2002).

See pathway and interaction figures.

The structure of GSK3 beta has been determined, and there is structural information on the GSK-Axin complex (Dajani 2003)

Human	mouse	mouse phenotype	Drosophila
GSK3a	Gsk3a	Double with GSK3b, ES cell differentiation phenotypes Doble 2007 Double with GSK3b hyperproliferation of neural progenitors (Kim et al, 2009)	Shaggy/Zeste-white 3
GSK3 b	GSK3b	phenotype Cleft palate in conditional KO (Liu, 2007) Double with GSK3a hyperproliferation of neural progenitors (Kim et al, 2009)

Human

mouse

mouse phenotype

Drosophila

GSK3a

Gsk3a

Double with GSK3b, ES cell differentiation phenotypes Doble 2007

Double with GSK3b hyperproliferation of neural progenitors (Kim et al, 2009)

Cleft palate in conditional KO (Liu, 2007)

Double with GSK3a hyperproliferation of neural progenitors (Kim et al, 2009)