Su Y C, Treisman J E, Skolnik E Y
Department of Pharmacology, New York University Medical Center, Skirball Institute of Biomolecular Medicine, New York, New York 10016 USA.
Genes Dev. 1998 Aug 1;12(15):2371-80. doi: 10.1101/gad.12.15.2371.
Dorsal closure in the Drosophila embryo occurs during the later stages of embryogenesis and involves changes in cell shape leading to the juxtaposition and subsequent adherence of the lateral epidermal primordia over the amnioserosa. Dorsal closure requires the activation of a conserved c-jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) module, as it is blocked by null mutations in JNK kinase [hemipterous (hep)] and JNK [basket (bsk)]. Drosophila JNK (DJNK) functions by phosphorylating and activating DJun, which in turn induces the transcription of decapentaplegic (dpp). We provide biochemical and genetic evidence that a Ste20-related kinase, misshapen (msn), functions upstream of hep and bsk to stimulate dorsal closure in the Drosophila embryo. Mammalian (NCK-interacting kinase [NIK]) and Caenorhabditis elegans (mig-15) homologs of msn have been identified; mig-15 is necessary for several developmental processes in C. elegans. These data suggest that msn, mig-15, and NIK are components of a signaling pathway that is conserved among flies, worms, and mammals to control developmentally regulated pathways.
果蝇胚胎的背侧闭合发生在胚胎发育后期，涉及细胞形状的变化，导致外侧表皮原基在羊膜上并列并随后黏附。背侧闭合需要激活保守的c-jun氨基末端激酶（JNK）丝裂原活化蛋白激酶（MAPK）模块，因为它会被JNK激酶[半翅目（hep）]和JNK[篮状（bsk）]的无效突变所阻断。果蝇JNK（DJNK）通过磷酸化并激活DJun发挥作用，而DJun反过来又诱导果蝇dpp基因的转录。我们提供了生化和遗传学证据，表明一种与Ste20相关的激酶，畸形（msn），在hep和bsk的上游发挥作用，以刺激果蝇胚胎的背侧闭合。已经鉴定出msn的哺乳动物（NCK相互作用激酶[NIK]）和秀丽隐杆线虫（mig-15）同源物；mig-15是秀丽隐杆线虫几个发育过程所必需的。这些数据表明，msn、mig-15和NIK是在果蝇、线虫和哺乳动物中保守的信号通路的组成部分，用于控制发育调控的通路。
