Glycogen synthase kinase-3b (GSK-3b), a serine/threonine protein kinase, is one of two mammalian GSK-3 isoforms, designated GSK-3a (Mr=51kD) and GSK-3b (Mr=47kD). The two isoforms map to different genes: in humans, GSK-3a maps to 19q13.2, while GSK-3b maps to 3q13.3. The kinase domains of the two isoforms share the greatest homology (approximately 95% homology), while the C-terminal regions are found to diverge between the two isoforms (36% homology). The two isoforms also differ slightly in structure. GSK-3a contains a glycine-rich extension in its N-terminus that is absent from GSK-3b, a feature that accounts for the difference in the molecular masses of the two isoforms. GSK-3b homologs appear to be ubiquitously expressed in eukaryotes. The Drosophila homolog is designated Shaggy/Zeste-white3. The GSKs were initially identified as negative regulators of glycogen synthase, a key enzyme in glycogen metabolism. Recent studies have revealed that GSK-3b also phosphorylates numerous other