He Ying, Emoto Kazuo, Fang Xiaolan, Ren Nan, Tian Xiaojing, Jan Yuh-Nung, Adler Paul N
Department of Biology, Center for Morphogenesis and Regenerative Medicine and Cancer Center, University of Virginia, Charlottesville, VA 22903, USA.
Mol Biol Cell. 2005 Sep;16(9):4139-52. doi: 10.1091/mbc.e05-01-0018. Epub 2005 Jun 22.
The function of Tricornered (Trc), the Drosophila Ndr (Nuclear Dbf2-related) serine/threonine protein kinase, is required for the normal morphogenesis of a variety of polarized outgrowths including epidermal hairs, bristles, arista laterals, and dendrites. In yeast the Trc homolog Cbk1 needs to bind Mob2 to activate the RAM pathway. In this report, we provide genetic and biochemical data that Drosophila Trc also interacts with and is activated by Drosophila Dmob proteins. In addition, Drosophila Mob proteins appear to interact with the related Warts/Lats kinase, which functions as a tumor suppressor in flies and mammals. Interestingly, the overgrowth tumor phenotype that results from mutations in Dmob1 (mats) was only seen in genetic mosaics and not when the entire animal was mutant. We conclude that unlike in yeast, in Drosophila individual Mob proteins interact with multiple kinases and that individual NDR family kinases interact with multiple Mob proteins. We further provide evidence that Mo25, the Drosophila homolog of the RAM pathway hym1 gene does not function along with Trc.
果蝇Ndr(核Dbf2相关)丝氨酸/苏氨酸蛋白激酶三角帽蛋白(Trc)的功能,对于包括表皮毛、刚毛、触角侧支和树突在内的多种极化性生长物的正常形态发生是必需的。在酵母中,Trc同源物Cbk1需要与Mob2结合以激活RAM途径。在本报告中,我们提供了遗传和生化数据,表明果蝇Trc也与果蝇Dmob蛋白相互作用并被其激活。此外,果蝇Mob蛋白似乎与相关的疣蛋白/大肿瘤抑制蛋白激酶相互作用,该激酶在果蝇和哺乳动物中作为肿瘤抑制因子发挥作用。有趣的是,Dmob1(mats)突变导致的过度生长肿瘤表型仅在遗传嵌合体中出现,而在整个动物均为突变体时未出现。我们得出结论,与酵母不同,在果蝇中单个Mob蛋白与多种激酶相互作用,单个NDR家族激酶与多种Mob蛋白相互作用。我们进一步提供证据表明,RAM途径hym1基因的果蝇同源物Mo25不与Trc一起发挥作用。