Abstract
The GSK-3 family of serine/threonine kinases, which is comprised of two isoforms (α and β), was initially identified as a negative regulator of glycogen synthase, the rate limiting enzyme of glycogen synthesis [1,2]. In the 30. years since its initial discovery, the family has been reported to regulate a host of additional cellular processes and, consequently, disease states such as bipolar disorders, diabetes, inflammatory diseases, cancer, and neurodegenerative diseases including Alzheimer's Disease and Parkinson's Disease [3,4]. As a result, there has been intense interest on the part of the pharmaceutical industry in developing small molecule antagonists of GSK-3. Herein, we will review the roles played by GSK-3s in the heart, focusing primarily on recent studies that have employed global and tissue-specific gene deletion. We will highlight roles in various pathologic processes, including pressure overload and ischemic injury, focusing on some striking isoform-specific effects of the family. Due to space limitations and/or the relatively limited data in gene-targeted mice, we will not be addressing the family's roles in ischemic pre-conditioning or its many interactions with various pro- and anti-apoptotic factors. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure".
Original language | English (US) |
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Pages (from-to) | 607-613 |
Number of pages | 7 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 51 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2011 |
Externally published | Yes |
Keywords
- Cardiac hypertrophy
- Glycogen synthase kinase 3
- Metabolism
- Therapeutic potential
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine