Downstream of growth factor receptors, signaling by the phosphoinositide 3 kinase (PI3K) pathway is known to play an important role in the growth and survival of many tumor types. The PI3K pathway simplistically comprises PI3K itself, followed by PDK-1, then AKT and finally glycogen synthase kinase 3 (GSK3). PI3K/AKT signaling promotes increased GSK3 phosphorylation, that is associated with reduced GSK3 activity. There are two isoforms of GSK3, GSK3α and GSK3β, which have a high degree of sequence homology. GSK3 plays a role not only in the regulation of glycogen synthase activity but in the expression of multiple other proteins that play a role in cancer biology, including cyclins and anti-apoptotic proteins.
Keywords: AR-A014418; GSK3; apoptosis; neuroblastoma.