Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins
Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins
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DOI：
10.1126/science.1084174
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发表时间：
2003-09-19
期刊：
影响因子：
56.9
通讯作者：
Springer, TA
中科院分区：
文献类型：
--
作者：
Kim, M;Carman, CV;Springer, TA
尽管整合素对发育、免疫、伤口愈合和转移至关重要，但它是为数不多的几类质膜受体之一，其基本信号机制仍然是一个谜。我们通过测量青色荧光蛋白融合蛋白与黄色荧光蛋白融合蛋白融合蛋白α(L)和β(2)胞质结构域之间的荧光共振能量转移，研究了活细胞中整合素LFA-1(α(L)β(2))的胞质构象变化。在静息状态下，这些结构域彼此接近，但无论是细胞内整合素粘附性的激活(由内向外信号)还是配体结合(由外向内信号)的激活，都经历了显著的空间分离。因此，双向整合素信号是通过将细胞外构象变化耦合到α和β细胞质结构域的解锁和分离来完成的，这是跨质膜传递信息的一种独特机制。
Although critical for development, immunity, wound healing, and metastasis, integrins represent one of the few classes of plasma membrane receptors for which the basic signaling mechanism remains a mystery. We investigated cytoplasmic conformational changes in the integrin LFA-1 (alpha(L)beta(2)) in living cells by measuring fluorescence resonance energy transfer between cyan fluorescent protein - fused and yellow fluorescent protein - fused alpha(L) and beta(2) cytoplasmic domains. In the resting state these domains were close to each other, but underwent significant spatial separation upon either intracellular activation of integrin adhesiveness (inside-out signaling) or ligand binding (outside-in signaling). Thus, bidirectional integrin signaling is accomplished by coupling extracellular conformational changes to an unclasping and separation of the alpha and beta cytoplasmic domains, a distinctive mechanism for transmitting information across the plasma membrane.