anti-Phospho-GSK-3beta (Ser9), Rabbit Monoclonal (RM453)

Glycogen synthase kinase-3 (GSK3) is a protein kinase that was originally identified as a regulator of glycogen synthase, a key enzyme in glycogen metabolism. Since then, it has been shown to be involved in the regulation of a diverse array of cellular functions, including protein synthesis, cell proliferation, cell differentiation, microtubule assembly/disassembly and apoptosis. GSK3's substrate specificity is unique in that phosphorylation of the substrate only occurs if a phosphoserine or phosphotyrosine is present - four residues C-terminal to the site of GSK phosphorylation. There exist two isoforms of GSK3, GSK3-α and GSK3-β, and they are strictly regulated via phosphorylation. Phosphorylation of GSK3-β on Ser9 (Ser21 in GSK3-α) by protein kinase B (PKB) causes its inactivation and is the primary mechanism responsible for growth factor inhibition of this kinase. Activation of GSK3-β is dependent upon the phosphorylation of Tyr216 (Tyr279 in GSK3-α). Upon activation, it has been shown to phosphorylate a number of different cellular proteins, including p53, c-Myc, c-Jun, heat shock factor-1 (HSF-1) and cyclin D1. GSK3-β also has been shown to phosphorylate aberrant sites on the microtubule associated protein tau, which is critical for the progression of Alzheimer's disease.