Regulation of cell proliferation by interleukin-3-induced nuclear translocation of pyruvate kinase
Regulation of cell proliferation by interleukin-3-induced nuclear translocation of pyruvate kinase
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DOI：
10.1074/jbc.m700094200
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发表时间：
2007-06-15
影响因子：
4.8
通讯作者：
Fujii, Hodaka
中科院分区：
文献类型：
--
作者：
Hoshino, Akemi;Hirst, John A.;Fujii, Hodaka
与细胞表面受体结合的细胞外信号分子可以调节核功能，从而影响细胞增殖、分化和功能。为了调节核功能，信号必须穿过核膜转导，以将信号从细胞质传播到细胞核。因此，许多信号应答诱导转录因子、激酶等的核转位。通过使用诱导易位陷阱，报告基因为基础的系统，以检测诱导核易位，我们发现，M2亚型的丙酮酸激酶，糖酵解的关键酶，易位到细胞核的白细胞介素-3，但不是由表皮生长因子，刺激。丙酮酸激酶M2亚型的C结构域足以进行白细胞介素-3诱导的核转位。白细胞介素-3诱导的丙酮酸激酶M2亚型的核转位依赖于Jak2的激活。过表达的M2亚型的丙酮酸激酶蛋白融合的核定位信号增强细胞增殖的情况下，白细胞介素-3，这表明核丙酮酸激酶在细胞增殖中起着重要的作用。
Extracellular signaling molecules bound to cell surface receptors can regulate nuclear function with consequences for cell proliferation, differentiation, and function. To regulate nuclear function, signals must be transduced across the nuclear envelope to propagate the signal from the cytoplasm to the nucleus. Therefore, many signaling responses induce the nuclear translocation of transcription factors, kinases, and others. By using inducible translocation trap, a reporter gene-based system to detect inducible nuclear translocation, we found that the M2 isoform of pyruvate kinase, a key enzyme in glycolysis, translocates into the nucleus by interleukin-3, but not by epidermal growth factor, stimulation. The C domain of the M2 isoform of pyruvate kinase was sufficient for interleukin-3-induced nuclear translocation. Interleukin-3-induced nuclear translocation of the M2 isoform of pyruvate kinase was dependent on the activation of Jak2. Overexpression of the M2 isoform of pyruvate kinase protein fused with a nuclear localization signal enhanced cell proliferation in the absence of interleukin-3, suggesting that the nuclear pyruvate kinase plays an important role in cell proliferation.