Glycogen synthase kinase-3 (GSK-3): Technical Overview Glycogen synthase kinase-3 (GSK-3), a multifunctional serine/threonine kinase, is a key regulator of numerous signaling pathways. Two isoforms of GSK-3 are reported in mammals: a 51 kDa GSK-3a and a 47 kDa GSK-3b. These two isoforms exhibit about 98% homology in their kinase domains, but share only about 36% identity in the last 76 C-terminal amino acid residues. GSK-3a contains a glycine-rich extension at its N-terminus. A minor (~15% of total) splice variant of GSK-3b, GSK-3b2, has also been identified, which contains a 13-residue insert within the kinase domain. It exhibits reduced kinase activity towards tau protein compared with ‘unspliced’ GSK-3b. GSK-3b2 is localized primarily to neuronal cell bodies, unlike unspliced GSK-3b that is also found in neuronal processes. Read more...