Journal
GENES & DEVELOPMENT
Volume 19, Issue 17, Pages 2066-2077Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1338705
Keywords
myocyte enhancer factor 2; transcriptional regulation; serine arginine protein kinase (SRPK); Stk23/Srpk3; centronuclear myopathy
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Funding
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008014] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL083488] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008014, T-32-GM08014] Funding Source: Medline
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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.
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