Glycogen synthase kinase-3beta: a novel regulator of cardiac hypertrophy and development.
Glycogen synthase kinase-3beta (GSK-3beta) is a ubiquitously expressed constitutively active serine/threonine kinase that phosphorylates cellular substrates and thereby regulates a wide variety of cellular functions, including development, metabolism, gene transcription, protein translation, cytoskeletal organization, cell cycle regulation, and apoptosis. The activity of GSK-3beta is negatively regulated by protein kinase B/Akt and by the Wnt signaling pathway. Increasing lines of evidence show that GSK-3beta is an essential negative regulator of cardiac hypertrophy and that the inhibition of GSK-3beta by hypertrophic stimuli is an important mechanism contributing to the development of cardiac hypertrophy. GSK-3beta also plays an important role in regulating cardiac development. In this review, the role of GSK-3beta in cardiac hypertrophy and development and the potential underlying mechanisms are discussed.
Hardt
Stefan E
SE
Department of Cell Biology and Molecular Medicine, Department of Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark.
Sadoshima
Junichi
J
D000818:Animals; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D006332:Cardiomegaly / Q000201:enzymology* / Q000209:etiology; D002453:Cell Cycle; D003599:Cytoskeleton / Q000648:ultrastructure; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D008954:Models, Biological; D009206:Myocardium / Q000201:enzymology*; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3