GSK-3

• OMIM: 606784
• UniProt: P49840

Glycogen synthase kinase 3 (GSK -3) is a serine / threonine protein kinase, that is a protein which selectively attach phosphate residues of the serine and threonine residues of other proteins (in this case, it is the glycogen synthase ). The phosphorylation of specific target proteins by GSK- 3 inhibits this usually.

Function

GSK -3 phosphorylates glycogen synthase, which is thereby inactivated. GSK- 3 thus plays a role in the regulation of glycogen synthesis. In the fruit fly Drosophila melanogaster and the clawed frog Xenopus laevis, the GSK -3 (here: GSK- 3β ) involved in signal transduction in the Wnt signaling pathway. The kinase cooperates in a protein complex together with Adenomatous polyposis coli - protein ( APC ) and the scaffolding protein Axin and phosphorylates the protein β - catenin. This leads to the ubiquitination and degradation of β -catenin by proteases, which makes it not penetrate into the cell nucleus, where it can perform its gene regulatory function. However, if the protein Disheveled is activated via the Wnt pathway, GSK - 3 itself is inactivated and β -catenin accumulates in the cytoplasm and in the nucleus, where it exerts its regulatory function and Wnt target genes activated.

Research at Stanford University and at the University of Karlsruhe showed that the inhibition of GSK- 3 by LiCl for example for the treatment of breast cancer and mixed lineage leukemia (MLL ), a type of blood cancer can serve.

GSK-3 deactivation

GSK -3 can be phosphorylated by the protein kinase B and thus deactivated. Thus, PKB ( Protein Kinase B) is an activator of signal transduction pathways which are normally blocked by the GSK-3.