Find GSK3A Products Interaction Network for GSK3A GSK3A Details

Related Pathways PTEN Signaling Insulin Receptor Signaling P13K / AKT Signaling View All Pathways

Synonyms: DKFZp686D0638, GSK3 ALPHA, GSK3A

GSK3 Signaling Pathway

Glycogen synthase kinase-3, GSK3, isoforms GSK-3a and GSK-3b, are constitutively active serine/threonine protein kinases involved in the regulation of WNT signaling (wingless pathway) (b-catenin); initiation of protein translation (eIF2B); glycogen synthesis (glycogen synthase, GS); promotion of mitochondrial apoptosis (Bax) and other signaling elements such as cyclin D1, heat shock factor-1 (HSF-1), c-jun and p53. GSK3 is involved in the regulation of a wide range of additional cell factors and responses.

Active GSK-3b promotes beta-catenin degradation and inhibits protein synthesis. Beta-catenin is the penultimate downstream mediator of WNT signaling. In the nucleus it interacts as a coactivator with lymphoid enhancer factor/T cell factor (Lef/Tcf) transcription factors. GSK-3b phosphorylates and promotes the betaTrCP (beta-Transducin repeat containing protein) targeted ubiquitin-proteosome pathway degradation of beta-catenin (b inhibits protein synthesis by phosphorylating eIF2Bepsilon, a subunit of eIF2B.

The degradation of beta-catenin and inhibition of protein synthesis are suppressed by the phosphorylation of GSK-3b. GSK-3b is phosphorylated by a number of kinases. Among these are Akt/PKB and MAPKAP-K1 (aka RSK-2; p90rsk) which are activated by a PI3K-PDK-PKB(Akt) and Ras-Raf-MEK-MAPK (ERK1, ERK 2, ERK 3 and ERK-5)-RSK2 pathways, respectively.