A Mutation in PRKAG3 Associated with Excess Glycogen Content in Pig Skeletal Muscle

作者：Denis Milan, Jin‐Tae Jeon, Christian Looft, Valérie Amarger, Annie Robic, M. Thelander, Claire Rogel Gaillard, Sven Paul, Nathalie Iannuccelli, Lars Rask, Hans Ronne, Kerstin Lundström, N. Reinsch, Joël Gellin, E. Kalm, Pascale Le Roy, Patrick Chardon, Leif Andersson · 发表于：Science · 年份：2000 · DOI：10.1126/science.288.5469.1248 · 被引用次数：732 · 研究领域：Metabolism, Diabetes, and Cancer、Protein Kinase Regulation and GTPase Signaling、PI3K/AKT/mTOR signaling in cancer

A high proportion of purebred Hampshire pigs carries the dominant RN- mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast (SNF4) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis.