Role of glycogen synthase kinase-3 in XXXX : regulation by Wnts and other signaling pathways.

@entity1 @entity22596 @entity4357 @entity5 @entity563 @entity1889 @entity238
Although glycogen synthase kinase-3 ( @entity22596 ) is but one of more than a thousand distinct @entity563 / @entity1889 kinases present in the @entity1 genome, this enzyme has attracted attention for its role in a diverse range of cellular processes and its positioning at a nexus of several signaling pathways that are important in @entity5 and other @entity1 diseases. The association of @entity22596 with widely different functions, from glycogen metabolism to @entity238 segmentation and slime mold differentiation, was initially perplexing. However, as the context of the biological processes involving this enzyme has been clarified, unifying themes have emerged that begin to explain its pleiotropic nature. Unlike most protein kinases involved in signaling, @entity22596 is active in unstimulated, resting cells. Its activity is inactivated during cellular responses and its substrates therefore tend to be dephosphorylated. As more of these targets have been identified and the effects of their modification by @entity22596 determined, most have been found to be functionally inhibited by @entity22596 . Hence, this kinase appears to act as a general repressor, keeping its targets switched off or inaccessible under resting conditions. The rarity of this form of regulation is perhaps related to the diversity of its targets. Over the past decade, the importance of @entity22596 has been established by three significant properties: its remarkable evolutionary conservation, allowing analysis in genetically tractable organisms; its involvement in the Wnt/wingless signaling pathway; and its inhibition by agonists of the prosurvival @entity4357 3' kinase (P13'K) pathway. This review covers recent advances in understanding the physiological roles of this enzyme, particularly in the context of @entity5 .
