Marks A R
Laboratory of Molecular Cardiology, Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, USA.
Physiol Rev. 1996 Jul;76(3):631-49. doi: 10.1152/physrev.1996.76.3.631.
Immunophilins are members of a highly conserved family of proteins all of which are cis-trans peptidyl-prolyl isomerases. The prototypic members of the immunophilin family, cyclophilin A and FKPB12, were discovered on the basis of their ability to bind and mediate the immunosuppressive effects of the drugs cyclosporin, FK506, and rapamycin. However, the prolyl isomerase activity of these proteins is not involved in any of the immunosuppressive effects. Indeed, despite the fact that all members of the family are prolyl isomerases, the cellular role of this enzymatic function has not been clearly defined. In many cases, immunophilins are widely expressed and are present at high levels in some tissues. Moreover, while the number of proteins that belong to the immunophilin family continues to grow, the natural cellular functions of all but a few remain obscure. An example where immunophilins do appear to have a defined cellular role, in the absence of immunosuppressive ligands, is the modulation of intracellular calcium release channel function by FKBP12 and FKBP12.6. In this case, FKBPs are integral parts of three types of calcium release channel complexes, skeletal and cardiac ryanodine receptors and the inositol 1,4,5-trisphosphate receptor. In each case, FKBPs modulate channel function possibly by enhancing the cooperativity between subunits.
亲免素是一类高度保守的蛋白质家族成员，它们均为顺反肽基脯氨酰异构酶。亲免素家族的典型成员，亲环蛋白A和FKBP12，是基于它们结合并介导环孢素、FK506和雷帕霉素等药物免疫抑制作用的能力而被发现的。然而，这些蛋白质的脯氨酰异构酶活性并不参与任何免疫抑制作用。实际上，尽管该家族所有成员都是脯氨酰异构酶，但这种酶功能的细胞作用尚未明确界定。在许多情况下，亲免素广泛表达且在某些组织中含量很高。此外，虽然属于亲免素家族的蛋白质数量持续增加，但除少数几种外，其他所有蛋白质的天然细胞功能仍不清楚。在没有免疫抑制配体的情况下，亲免素似乎确实具有明确细胞作用的一个例子是FKBP12和FKBP12.6对细胞内钙释放通道功能的调节。在这种情况下，FKBP是三种类型钙释放通道复合物的组成部分，即骨骼肌和心肌兰尼碱受体以及肌醇1,4,5 -三磷酸受体。在每种情况下，FKBP可能通过增强亚基之间的协同作用来调节通道功能。
