Glycogen synthase kinase-3 (GSK-3) is an unusual protein-serine kinase in that it is primarily regulated by inhibition and lies downstream of multiple cell signaling pathways. Cloning of GSK-3 first revealed it to comprise two distinct genes (termed α and β) that are highly homologous.  GSK-3α has a molecular weight of 51 kDa, whereas GSK-3β is smaller at 47 kDa. As its name implies, GSK-3α and GSK-3β fall into the CMGC (containing CDK, MAPK, GSK-3, CLK families) group of protein kinases.  GSK-3 is an ubiquitously expressed protein with both gene products expressed in all mammalian tissues. Similar to MAPKs, GSK-3 is phosphorylated (constitutively) in its active state at tyrosine 216 (GSK-3β) and tyrosine 279 (GSK-3α). Insulin, growth factors, or certain amino acids can trigger inactivation of GSK-3 through phosphorylation at serine 21 (GSK-3α) or serine 9 (GSK-3β) through the action of kinases such as AKT/PKB, p90rsk, and p70rsk. GSK-3 also plays roles in other signaling pathways: Wnt Signaling, Notch Signaling, Hedgehog Signaling and Transforming Growth Factor β Signaling.


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