Bild Andrea H, Turkson James, Jove Richard
Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
EMBO J. 2002 Jul 1;21(13):3255-63. doi: 10.1093/emboj/cdf351.
Signal transducer and activator of transcription (STAT) proteins are cytoplasmic transcription factors that translocate to the nucleus and regulate gene expression upon activation of cytokine or growth factor receptors. While this translocation event is essential for gene regulation by STATs, their mechanism of transport through the cytoplasm to the nucleus has remained elusive. We now report that cytoplasmic transport of Stat3 is an active process that requires receptor-mediated endocytosis. Stat3 co-localizes with endocytic vesicles in transit from the cell membrane to the perinuclear region in response to growth factor stimulation. Consistent with a role for receptor endocytosis in growth factor signaling, disruption of endocytosis with specific inhibitors blocks Stat3 nuclear translocation and Stat3-dependent gene regulation. These results indicate that receptor-mediated endocytosis may be a general mechanism of transport through the cytoplasm for a subset of cytoplasmic signaling proteins destined for the nucleus.
信号转导与转录激活因子（STAT）蛋白是细胞质转录因子，在细胞因子或生长因子受体激活后会转移至细胞核并调节基因表达。虽然这种转位事件对于STATs调节基因至关重要，但其通过细胞质运输到细胞核的机制仍不清楚。我们现在报告，Stat3的细胞质运输是一个活跃过程，需要受体介导的内吞作用。响应生长因子刺激，Stat3与从细胞膜转运至核周区域的内吞小泡共定位。与受体内吞作用在生长因子信号传导中的作用一致，用特异性抑制剂破坏内吞作用会阻断Stat3核转位和Stat3依赖性基因调节。这些结果表明，受体介导的内吞作用可能是一部分 destined for the nucleus的细胞质信号蛋白通过细胞质运输的一般机制。 （注：原文中“destined for the nucleus”表述不太完整准确，可能影响译文最后一句理解，但按要求未作修改）
