Glycogen synthase kinase 3: a key regulator of cellular fate.
The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified as a key regulator of insulin-dependent glycogen synthesis. GSK-3 was subsequently shown to function in a wide range of cellular processes including differentiation, growth, motility and apoptosis. Aberrant regulation of GSK-3 has been implicated in a range of human pathologies including Alzheimer's disease, non-insulin-dependent diabetes mellitus (NIDDM) and cancer. As a consequence, the regulation of GSK-3 and the therapeutic potential of GSK-3 inhibitors have become key areas of investigation. This review will focus on the mechanisms of GSK-3 regulation, with emphasis on modulation by upstream signals, control of substrate specificity and GSK-3 localisation. The details of these mechanisms will be discussed in the context of specific signalling pathways.
Forde
J E
JE
Biomedical Sciences Building, Cardiff School of Biosciences, Museum Avenue, CF10 3US, Cardiff, UK.
Dale
T C
TC
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D006003:Glycogen / Q000096:biosynthesis; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D053823:Hedgehog Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D006003:Glycogen; D038362:Glycogen Synthase Kinase 3