Mitcham J L, Parnet P, Bonnert T P, Garka K E, Gerhart M J, Slack J L, Gayle M A, Dower S K, Sims J E
Immunex Corporation, Seattle, Washington 98101, USA.
J Biol Chem. 1996 Mar 8;271(10):5777-83. doi: 10.1074/jbc.271.10.5777.
Through data base searches, we have discovered new proteins that share homology with the signaling domain of the type I interleukin-1 receptor (IL-1RI): human "randomly sequenced cDNA 786" (rsc786), murine MyD88, and two partial Drosophila open reading frames, MstProx and STSDm2245. Comparisons between these new proteins and known IL-1RI homologous proteins such as Toll, 18-Wheeler, and T1/ST2 revealed six clusters of amino acid similarity. We tested the hypothesis that sequence similarity between the signaling domain of IL-1RI and the three mammalian family members might indicate functional similarity. Chimeric IL-1RI receptors expressing the putative signaling domains of T1/ST2, MyD88, and rsc786 were assayed by three separate IL-1 responsive assays, NF-kappaB, phosphorylation of an epidermal growth factor receptor peptide, and an interleukin 8 promoter-controlled reporter construct, for their ability to transduce an IL-1-stimulated signal. All three assays were positive in response to the T1/ST2 chimera, while the MyD88 and rsc786 chimeras failed to respond. These data indicate that the sequence homology between IL-1RI and T1/ST2 indicates a functional homology as well.
通过数据库搜索，我们发现了与I型白细胞介素-1受体（IL-1RI）信号结构域具有同源性的新蛋白质：人类“随机测序cDNA 786”（rsc786）、小鼠MyD88以及果蝇的两个部分开放阅读框MstProx和STSDm2245。这些新蛋白质与已知的IL-1RI同源蛋白质（如Toll、18-Wheeler和T1/ST2）之间的比较揭示了六个氨基酸相似性簇。我们检验了这样一个假设，即IL-1RI信号结构域与三个哺乳动物家族成员之间的序列相似性可能表明功能相似性。通过三种独立的IL-1反应性测定法对表达T1/ST2、MyD88和rsc786假定信号结构域的嵌合IL-1RI受体进行了检测，这三种测定法分别是NF-κB、表皮生长因子受体肽的磷酸化以及白细胞介素8启动子控制的报告基因构建体，以检测它们转导IL-1刺激信号的能力。所有三种测定法对T1/ST2嵌合体均呈阳性反应，而MyD88和rsc786嵌合体则无反应。这些数据表明，IL-1RI与T1/ST2之间的序列同源性也表明了功能同源性。
