Gay Nicholas J, Gangloff Monique
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
Annu Rev Biochem. 2007;76:141-65. doi: 10.1146/annurev.biochem.76.060305.151318.
The Toll family of class I transmembrane receptors recognizes and responds to diverse structures associated with pathogenic microorganisms. These receptors mediate initial responses in innate immunity and are required for the development of the adaptive immune response. Toll receptor signaling pathways are also implicated in serious autoimmune diseases such as endotoxic shock and thus are important therapeutic targets. In this review we discuss how microbial structures as different as nucleic acids and lipoproteins can be recognized by the extracellular domains of Toll receptors. We review recent evidence that the mechanism of signal transduction is complex and involves sequential changes in the conformation of the receptor induced by binding of the ligand. Finally, we assess the emerging area of cross talk in the Toll pathways. Recent work suggests that signaling through TLR4 in response to endotoxin is modified by inputs from at least two other pathways acting through beta2 integrins and protein kinase Cepsilon.
I类跨膜受体的Toll家族能够识别与致病微生物相关的多种结构并作出反应。这些受体介导先天免疫的初始反应，也是适应性免疫反应发展所必需的。Toll受体信号通路还与诸如内毒素休克等严重自身免疫性疾病有关，因此是重要的治疗靶点。在这篇综述中，我们讨论了Toll受体的胞外结构域如何识别诸如核酸和脂蛋白等不同的微生物结构。我们回顾了最近的证据，即信号转导机制很复杂，涉及由配体结合诱导的受体构象的顺序变化。最后，我们评估了Toll通路中新兴的相互作用领域。最近的研究表明，对内毒素作出反应的通过TLR4的信号传导会受到至少另外两条通过β2整合素和蛋白激酶Cε起作用的通路的输入的影响。
