CONTROLLING SIGNAL-TRANSDUCTION WITH SYNTHETIC LIGANDS
CONTROLLING SIGNAL-TRANSDUCTION WITH SYNTHETIC LIGANDS
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DOI：
10.1126/science.7694365
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发表时间：
1993-11-12
期刊：
影响因子：
56.9
通讯作者：
CRABTREE, GR
中科院分区：
文献类型：
--
作者：
SPENCER, DM;WANDLESS, TJ;CRABTREE, GR
二聚化和寡聚化是有助于细胞膜受体、转录因子、囊泡融合蛋白和其他种类的细胞内和细胞外蛋白的激活的一般生物控制机制。设计了可渗透细胞的合成配体，其可用于控制特定蛋白质的细胞内寡聚化。为了证明它们的效用，这些配体用于诱导细胞表面受体的细胞内寡聚化，所述细胞表面受体缺乏它们的跨膜区和细胞外区，但含有细胞内信号传导结构域。将这些配体添加到培养的细胞中导致信号传递和特异性靶基因激活。配体的单体形式阻断了该途径。这种配体调节的信号转导通路的激活和终止的方法具有应用于任何需要精确控制信号转导通路的地方的潜力。
Dimerization and oligomerization are general biological control mechanisms contributing to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. Cell permeable, synthetic ligands were devised that can be used to control the intracellular oligomerization of specific proteins. To demonstrate their utility, these ligands were used to induce intracellular oligomerization of cell surface receptors that lacked their transmembrane and extracellular regions but contained intracellular signaling domains. Addition of these ligands to cells in culture resulted in signal transmission and specific target gene activation. Monomeric forms of the ligands blocked the pathway. This method of ligand-regulated activation and termination of signaling pathways has the potential to be applied wherever precise control of a signal transduction pathway is desired.