Abstract
Myocyte enhancer factor 2 (MEF2) plays essential roles in transcriptional control of muscle development. However, signaling pathways acting downstream of MEF2 are largely unknown. Here, we performed a microarray analysis using Mef2c-null mouse embryos and identified a novel MEF2-regulated gene encoding a muscle-specific protein kinase, Srpk3, belonging to the serine arginine protein kinase (SRPK) family, which phosphorylates serine/arginine repeat-containing proteins. The Srpk3 gene is specifically expressed in the heart and skeletal muscle from embryogenesis to adulthood and is controlled by a muscle-specific enhancer directly regulated by MEF2. Srpk3-null mice display a new entity of type 2 fiber-specific myopathy with a marked increase in centrally placed nuclei; while transgenic mice overexpressing Srpk3 in skeletal muscle show severe myofiber degeneration and early lethality. We conclude that normal muscle growth and homeostasis require MEF2-dependent signaling by Srpk3.
Original language | English (US) |
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Pages (from-to) | 2066-2077 |
Number of pages | 12 |
Journal | Genes and Development |
Volume | 19 |
Issue number | 17 |
DOIs | |
State | Published - Sep 1 2005 |
Keywords
- Centronuclear myopathy
- Myocyte enhancer factor 2
- Serine arginine protein kinase (SRPK)
- Stk23/Srpk3
- Transcriptional regulation
ASJC Scopus subject areas
- General Medicine