Trofimova M, Sprenkle A B, Green M, Sturgill T W, Goebl M G, Harrington M A
Department of Biochemistry, Indiana University, Indianapolis, Indiana 46202-5121, USA.
J Biol Chem. 1996 Jul 26;271(30):17609-12. doi: 10.1074/jbc.271.30.17609.
The NF-kappaB/c-Rel proteins are a family of evolutionarily conserved transcription factors activated during development that in the adult, mediate many processes including the immune response. A high degree of sequence similarity is shared between the NF-kappaB/c-Rel family of transcription factors and the Drosophila Dorsal protein as well as between its cytoplasmic inhibitor, IkappaBalpha, and the Drosophila Cactus protein. Genetic analyses of Dorsal have defined components of a signaling pathway for Dorsal activation, including a serine/threonine kinase, Pelle, placed upstream of Dorsal and Cactus. We demonstrate that this pathway is likely to be conserved in mammals by the isolation of a cDNA that encodes a novel mouse protein highly related to Pelle, mPLK (mouse Pelle-like protein kinase). Expression of mPLK mRNA is developmentally regulated in the mouse and in adult tissue mPLK expression is greatest in the liver, a tissue that expresses a high level of NF-kappaB. Recombinant mPLK produced in bacteria is a protein kinase capable of autophosphorylating and phosphorylating IkappaBalpha.
核因子κB/c-Rel蛋白是一类在进化过程中保守的转录因子家族,在发育过程中被激活,在成体中,介导包括免疫反应在内的许多过程。核因子κB/c-Rel转录因子家族与果蝇背蛋白(Dorsal protein)之间以及其细胞质抑制剂IκBα与果蝇仙人掌蛋白(Cactus protein)之间存在高度的序列相似性。对背蛋白的遗传学分析确定了背蛋白激活信号通路的组成成分,包括一种丝氨酸/苏氨酸激酶Pelle,它位于背蛋白和仙人掌蛋白的上游。我们通过分离一个编码与Pelle高度相关的新型小鼠蛋白mPLK(小鼠类Pelle蛋白激酶)的cDNA,证明该信号通路在哺乳动物中可能是保守的。mPLK mRNA的表达在小鼠发育过程中受到调控,在成体组织中,mPLK在肝脏中的表达最高,肝脏是一个表达高水平核因子κB的组织。在细菌中产生的重组mPLK是一种能够自磷酸化并磷酸化IκBα的蛋白激酶。