Siegel R M, Frederiksen J K, Zacharias D A, Chan F K, Johnson M, Lynch D, Tsien R Y, Lenardo M J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Science. 2000 Jun 30;288(5475):2354-7. doi: 10.1126/science.288.5475.2354.
Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand- independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.
编码死亡受体Fas异常形式的杂合突变在人类自身免疫性淋巴增殖综合征中主要干扰Fas诱导的淋巴细胞凋亡。发现这种效应并非取决于配体诱导的受体寡聚化，而是源于野生型和突变型Fas受体通过细胞外结构域中的特定区域进行的非配体依赖性相互作用。通过绿色荧光蛋白变体之间的荧光共振能量转移在活细胞中发现了预组装的Fas复合物。这些结果表明，预组装受体复合物的形成对于Fas信号传导和人类疾病中的显性干扰是必要的。
