Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA.
Cell Adh Migr. 2010 Apr-Jun;4(2):255-67. doi: 10.4161/cam.4.2.10746. Epub 2010 Apr 24.
Single-chain receptors and multi-chain immune recognition receptors (SRs and MIRRs, respectively) represent families of structurally related but functionally different surface receptors expressed on different cells. In contrast to SRs, a distinctive and common structural characteristic of MIRR family members is that the extracellular recognition domains and intracellular signaling domains are located on separate subunits. How extracellular ligand binding triggers MIRRs and initiates intracellular signal transduction processes is not clear. A novel model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, suggests that the homooligomerization of receptor intracellular signaling domains represents a necessary and sufficient condition for receptor triggering. In this review, I demonstrate striking similarities between a consensus model of SR signaling and the SCHOOL model of MIRR signaling and show how these models, together with the lessons learned from viral pathogenesis, provide a molecular basis for novel pharmacological approaches targeting inter- and intrareceptor transmembrane interactions as universal therapeutic targets for a diverse variety of immune and other disorders.
单链受体和多链免疫识别受体（分别为 SR 和 MIRR）分别代表结构相关但功能不同的表面受体家族，这些受体存在于不同的细胞上。与 SR 不同，MIRR 家族成员的一个独特且常见的结构特征是，细胞外识别域和细胞内信号转导域位于不同的亚基上。细胞外配体结合如何触发 MIRR 并启动细胞内信号转导过程尚不清楚。一种新的免疫信号模型，信号链同源寡聚化（SCHOOL）模型表明，受体细胞内信号域的同源寡聚化是受体触发的必要和充分条件。在这篇综述中，我展示了 SR 信号的共识模型与 MIRR 信号的 SCHOOL 模型之间的惊人相似之处，并展示了这些模型如何与病毒发病机制的经验教训一起，为靶向跨和 intrareceptor 跨膜相互作用的新型药理学方法提供了分子基础，这些方法可作为针对各种免疫和其他疾病的通用治疗靶点。
