Jin S, Shimizu M, Balasubramanyam A, Epstein H F
Departments of Neurology, the Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Cell Motil Cytoskeleton. 2000 Feb;45(2):133-48. doi: 10.1002/(SICI)1097-0169(200002)45:2<133::AID-CM5>3.0.CO;2-S.
DMPK, the product of the DM locus, is a member of the same family of serine-threonine protein kinases as the Rho-associated enzymes. In DM, membrane inclusions accumulate in lens fiber cells producing cataracts. Overexpression of DMPK in cultured lens epithelial cells led to apoptotic-like blebbing of the plasma membrane and reorganization of the actin cytoskeleton. Enzymatically active DMPK was necessary for both effects; inactive mutant DMPK protein did not produce either effect. Active RhoA but not constitutive GDP-state mutant protein produced similar effects as DMPK. The similar actions of DMPK and RhoA suggest that they may function in the same regulatory network. The observed effects of DMPK may be relevant to the removal of membrane organelles during normal lens differentiation and the retention of intracellular membranes in DM lenses.
DMPK是DM基因座的产物，与Rho相关酶属于丝氨酸-苏氨酸蛋白激酶的同一家族。在DM中，膜内含物在晶状体纤维细胞中积累，导致白内障。在培养的晶状体上皮细胞中过表达DMPK会导致质膜出现凋亡样泡状化以及肌动蛋白细胞骨架的重组。这两种效应都需要具有酶活性的DMPK；无活性的突变型DMPK蛋白不会产生任何一种效应。活性RhoA而非组成型GDP状态突变蛋白产生与DMPK相似的效应。DMPK和RhoA的相似作用表明它们可能在同一调节网络中发挥作用。DMPK观察到的效应可能与正常晶状体分化过程中膜细胞器的清除以及DM晶状体中细胞内膜的保留有关。
