Wissmann A, Ingles J, McGhee J D, Mains P E
University of Calgary, Department of Medical Biochemistry, Alberta, Canada.
Genes Dev. 1997 Feb 15;11(4):409-22. doi: 10.1101/gad.11.4.409.
We have identified two genes associated with the hypodermal cell shape changes that occur during elongation of the Caenorhabditis elegans embryo. The first gene, called let-502, encodes a protein with high similarity to Rho-binding Ser/Thr kinases and to human myotonic dystrophy kinase (DM-kinase). Strong mutations in let-502 block embryonic elongation, and let-502 reporter constructs are expressed in hypodermal cells at the elongation stage of development. The second gene, mel-11, was identified by mutations that act as extragenic suppressors of let-502. mel-11 encodes a protein similar to the 110- to 133-kD regulatory subunits of vertebrate smooth muscle myosin-associated phosphatase (PP-1M). We suggest that the LET-502 kinase and the MEL-11 phosphatase subunit act in a pathway linking a signal generated by the small GTP-binding protein Rho to a myosin-based hypodermal contractile system that drives embryonic elongation. LET-502 may directly regulate the activity of the MEL-11 containing phosphatase complex and the similarity between LET-502 and DM-kinase suggests a similar function for DM-kinase.
我们已经鉴定出两个与秀丽隐杆线虫胚胎伸长过程中发生的皮下细胞形状变化相关的基因。第一个基因称为let-502,编码一种与Rho结合丝氨酸/苏氨酸激酶以及人类强直性肌营养不良激酶(DM-激酶)高度相似的蛋白质。let-502中的强突变会阻断胚胎伸长,并且let-502报告基因构建体在发育伸长阶段的皮下细胞中表达。第二个基因mel-11是通过作为let-502的基因外抑制子的突变鉴定出来的。mel-11编码一种与脊椎动物平滑肌肌球蛋白相关磷酸酶(PP-1M)的110至133kD调节亚基相似的蛋白质。我们认为LET-502激酶和MEL-11磷酸酶亚基在一条将小GTP结合蛋白Rho产生的信号与驱动胚胎伸长的基于肌球蛋白的皮下收缩系统联系起来的途径中发挥作用。LET-502可能直接调节含MEL-11的磷酸酶复合物的活性,并且LET-502与DM-激酶之间的相似性表明DM-激酶具有类似的功能。