摘要
G 联合蛋白质的受体 kinase (GRK2 ) 2 是调整不同的膜 receptorsand 的重要 serine/threonine-kinase 细胞内部的蛋白质。在胚胎或成年苍蝇的果蝇 Gprk2 的变细导致了体的肌肉，纤维的损失，和不能飞行的 phenotype.In 的有缺点的区别脊椎动物， GRK2 hemizygous 老鼠少些，但是更包含了 hypertrophied 骨胳的肌肉纤维比野类型的 littermates.In C2C12 myoblasts ， GRK2 kinase缺乏的异种( K220R )的 overexpression 引起了房间 intoimmature myotubes 的早熟的区别，它在尺寸是更宽的并且包含了更多的熔化原子核，当时 GRK2 overexpression b 熔化事件由提高的 GRK2 层次支持了的损害 differentiationand 少数被 p38MAPK 异种概括，它能由 GRK2 模仿 p38MAPK 的 theinhibitory phosphorylation，而在表示 GRK2 观察的弄钝的区别面对 p38MAPK 小径的一个组成地活跃的在上游的激发器克隆 wasrescued。这些结果建议 thatbalanced GRK2 功能为一个及时、完全的 myogenic 过程是必要的。
G protein-coupled receptor kinase 2 （GRK2） is an important serine/threonine-kinase regulating different membrane receptors and intraceUular proteins. Attenuation of Drosophila Gprk2 in embryos or adult flies induced a defective differentiation of somatic muscles, loss of fibers, and a flightless phenotype. In vertebrates, GRK2 hemizygous mice contained less but more hypertrophied skeletal muscle fibers than wild-type littermates. In C2C12 myoblasts, overexpression of a GRK2 kinase-deficient mutant （K220R） caused precocious differentiation of ceUs into immature myotubes, which were wider in size and contained more fused nuclei, while GRK2 overexpression blunted differentiation. Moreover, p38MAPK and Akt pathways were activated at an earlier stage and to a greater extent in K220R-expressing cells or upon kinase downregulation, while the activation of both kinases was impaired in GRK2-overexpressing cells. The impaired differentiation and fewer fusion events promoted by enhanced GRK2 levels were recapitulated by a p38MAPK mutant, which was able to mimic the inhibitory phosphorylation of p38MAPK by GRK2, whereas the blunted differentiation observed in GRK2-expressing clones was rescued in the presence of a constitutively active upstream stimulator of the p38MAPK pathway. These results suggest that balanced GRK2 function is necessary for a timely and complete myogenic process.
