Greenfeder S A, Nunes P, Kwee L, Labow M, Chizzonite R A, Ju G
Department of Inflammation/Autoimmune Diseases, Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA.
J Biol Chem. 1995 Jun 9;270(23):13757-65. doi: 10.1074/jbc.270.23.13757.
A monoclonal antibody (mAb) was isolated that blocked the binding and bioactivity of both human and murine interleukin 1 beta (IL-1 beta) on murine IL-1 receptor-bearing cells. This mAb recognized a protein that was distinct from the Type I and Type II IL-1 receptors, suggesting that an additional protein exists that is involved in IL-1 biological responses. By expression cloning in COS-7 cells, we have isolated a cDNA from mouse 3T3-LI cells encoding this putative auxiliary molecule, which we term the IL-1 receptor accessory protein (IL-1R AcP). Sequence analysis of the cDNA predicts an open reading frame that encodes a 570-amino acid protein with a molecular mass of approximately 66 kDa. The IL-1R AcP is a member of the Ig superfamily by analysis of its putative extracellular domain and also bears limited homology throughout the protein to both Type I and Type II IL-1 receptors. Northern analysis reveals that murine IL-1R AcP mRNA is expressed in many tissues and appears to be regulated by IL-1. In mammalian cells expressing natural or recombinant Type I IL-1R and IL-1R AcP, the accessory protein forms a complex with the Type I IL-1R and either IL-1 alpha or IL-1 beta but not IL-1ra. The recombinant accessory protein also increases the binding affinity of the recombinant Type I IL-1R for IL-1 beta when the two receptor proteins are coexpressed. Therefore, the functional IL-1 receptor appears to be a complex composed of at least two subunits.
一种单克隆抗体（mAb）被分离出来，它能阻断人和鼠白细胞介素1β（IL-1β）与带有鼠IL-1受体的细胞的结合及生物活性。这种mAb识别一种不同于I型和II型IL-1受体的蛋白质，这表明存在一种额外的蛋白质参与IL-1的生物学反应。通过在COS-7细胞中进行表达克隆，我们从小鼠3T3-LI细胞中分离出一个cDNA，它编码这种假定的辅助分子，我们将其命名为IL-受体辅助蛋白（IL-1R AcP）。对该cDNA的序列分析预测了一个开放阅读框，其编码一个570个氨基酸的蛋白质，分子量约为66 kDa。通过对其假定的细胞外结构域的分析，IL-1R AcP是免疫球蛋白超家族的成员，并且在整个蛋白质中与I型和II型IL-1受体也有有限的同源性。Northern分析显示，鼠IL-1R AcP mRNA在许多组织中表达，并且似乎受IL-1调控。在表达天然或重组I型IL-1R和IL-1R AcP的哺乳动物细胞中，辅助蛋白与I型IL-1R以及IL-1α或IL-1β形成复合物，但不与IL-1ra形成复合物。当两种受体蛋白共表达时，重组辅助蛋白也增加了重组I型IL-1R对IL-1β的结合亲和力。因此，功能性IL-1受体似乎是一个至少由两个亚基组成的复合物。
