Glycogen synthase kinase-3 (alpha) and (beta) (GSK-3(alpha), (beta)) are serine/threonine kinases that regulate metabolic enzymes and transcription factors, which are responsible for coordinating processes such as glycogen synthesis and cell adhesion. GSK-3(beta) activity is also required for nuclear activity of Rel dimers, which mediate an anti-apoptotic response to TNF(alpha) in mice. GSK-3 catalytic kinase activity is controlled through differential phosphorylation of serine/threonine residues, which have an inhibitory effect, and tyrosine residues, which have an activating effect. Growth factor stimulation of mammalian cells expressing GSK-3(alpha) and GSK-3(beta) induces phosphorylation of Ser 21 and Ser 9, respectively through a phosphatidylinositol 3-kinase (PI 3-kinase)-protein kinase B (PKB) dependent pathway, thereby enhancing proliferative signals. Additionally, GSK-3 physically associates with cAMP-dependent protein kinase A (PKA), which phosphorylates Ser 21 of GSK-3(alpha) or Ser 9 of GSK-3(beta) and inactivates both forms