Unique and Overlapping Functions of GSK-3 Isoforms in Cell Differentiation and Proliferation and Cardiovascular Development*
- ‡Center for Translational Medicine, Cardiology Division, and Program in Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 and the §Department of Medical Biophysics, University of Toronto, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
- 1 To whom correspondence should be addressed. E-mail: thomas.force{at}jefferson.edu.
Abstract
Intensive study over the past 30 years has helped define the role of the GSK-3 (glycogen synthase kinase-3) family in a variety of physiological and pathophysiological processes. However, the majority of these studies have relied upon overexpression approaches or nonselective small molecule inhibitors. Herein, we examine recent data derived from studies in gene-targeted embryonic stem cells and knock-out mice in an attempt to define the role these protein kinases play in critical decisions made by stem/progenitor cells and by early lineage-committed cardiomyocytes during development.
Footnotes
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↵2 The abbreviations used are: KO, knock-out; ES, embryonic stem; BIO, 6-bromoindirubin-3′-oxime; LIF, leukemia inhibitory factor; BMP, bone morphogenetic protein; ERK, extracellular signal-regulated kinase; EBs, embryoid bodies; DKO, double knock-out; WT, wild-type; PI3K, phosphatidylinositol 3-kinase; PKB, protein kinase B.
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↵* This work was supported, in whole or in part, by National Institutes of Health Grants HL61688 and HL091799 from NHLBI (to T. F.). This work was also supported by Canadian Institutes of Health Research Grants MOP 12858 and 74711 (to J. R. W.). This minireview will be reprinted in the 2009 Minireview Compendium, which will be available in January, 2010.
- The American Society for Biochemistry and Molecular Biology, Inc.
