Circulation Research. 2002;90:1055-1063
doi: 10.1161/01.RES.0000018952.70505.F1
doi: 10.1161/01.RES.0000018952.70505.F1
© 2002 American Heart Association, Inc.
Reviews |
Glycogen Synthase Kinase-3ß
A Novel Regulator of Cardiac Hypertrophy and Development
From the Department of Cell Biology and Molecular Medicine, Department of Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark.
Correspondence to Junichi Sadoshima, MD, PhD, Cardiovascular Research Institute UMDNJ, New Jersey Medical School, 185 South Orange Ave, MSB G-609, Newark, NJ 07103-2714. E-mail sadoshju{at}umdnj.edu
Glycogen synthase kinase-3ß (GSK-3ß) 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-3ß is negatively regulated by protein kinase B/Akt and by the Wnt signaling pathway. Increasing lines of evidence show that GSK-3ß is an essential negative regulator of cardiac hypertrophy and that the inhibition of GSK-3ß by hypertrophic stimuli is an important mechanism contributing to the development of cardiac hypertrophy. GSK-3ß also plays an important role in regulating cardiac development. In this review, the role of GSK-3ß in cardiac hypertrophy and development and the potential underlying mechanisms are discussed.
Key Words: glycogen synthase kinase-3&bgr • hypertrophy • development • Akt • Wnt pathway
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