A serine/threonine protein kinase (GSK, EC 18.104.22.168) present in two isoforms, GSK3-α (483 aa) and -β (420 aa), that is constitutively active in resting cells and is a negative regulator in various intracellular signalling pathways. Levels of GSK are rapidly reduced by insulin and various growth factors, releasing a constraint, and GSK is involved in the control of glycogen metabolism and protein synthesis by insulin, the modulation of AP1 and CREB, the specification of cell fate in Drosophila and the regulation of dorsoventral patterning in Xenopus. In Drosophila GSK3 (zeste-white 3/shaggy) functions as a negative regulator of the Wnt/β-catenin pathway. GSK3 itself is regulated by PKB. GSK3 is identical to tau protein kinase I and may therefore be important in the phosphorylation of tau that is known to occur in the neurofibrillary tangles of Alzheimer's disease.
Subjects: Medicine and Health — Chemistry.