Colony-stimulating factor 1-induced Na+ influx into human monocytes involves activation of a pertussis toxin-sensitive GTP-binding protein.
Colony-stimulating factor 1-induced Na+ influx into human monocytes involves activation of a pertussis toxin-sensitive GTP-binding protein.
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DOI：
10.1016/s0021-9258(18)68189-x
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发表时间：
1988-10
期刊：
影响因子：
--
通讯作者：
K. Imamura;D. Kufe
中科院分区：
文献类型：
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作者：
K. Imamura;D. Kufe
集落刺激因子-1通过与一类高亲和力受体结合来调节单核细胞的存活、生长和分化。目前的研究表明，脑脊液-1与单核细胞膜的相互作用与GTP类似物的特异性结合增加2.4倍有关。对GTP-γS结合数据的Scatchard分析表明，脑脊液-1刺激GTP结合是通过增加可用位点的亲和力而不是数量。这种由CSF-1刺激的GTP结合也与GTP酶活性的增加有关。此外，CSF-1诱导的GTP酶活性对百日咳毒素敏感。我们还证明了CSF-1通过一种对阿米洛利敏感的机制，可能是Na+/H+反向转运，刺激Na+内流进入单核细胞。这种由CSF-1刺激的Na+内流与Na+，K+-ATPase活性的升高进一步相关。此外，CSF-1对Na+内流和Na+，K+-ATPase活性的刺激作用对百日咳毒素敏感。最后，我们证明了CSF-1诱导的增殖也是百日咳毒素敏感的事件。因此，本研究结果提示：1)CSF-1受体与百日咳毒素敏感的G蛋白有关；2)百日咳毒素敏感的G蛋白参与了CSF-1诱导的Na+内流。
Colony-stimulating factor 1 (CSF-1) regulates the survival, growth, and differentiation of monocytes through binding to a single class of high affinity receptors. The present studies demonstrate that the interaction of CSF-1 with monocyte membranes is associated with a 2.4-fold increase in specific binding of the GTP analogue, GTP gamma S. Scatchard analysis of the GTP gamma S binding data indicated that CSF-1 stimulates GTP binding by increasing the affinity, rather than the number, of available sites. This stimulation of GTP binding by CSF-1 was also associated with an increase in GTPase activity. Furthermore, the CSF-1-induced stimulation of GTPase activity was sensitive to pertussis toxin. We also demonstrate that CSF-1 stimulates Na+ influx into monocytes by an amiloride-sensitive mechanism, presumably the Na+/H+ antiport. This CSF-1-stimulated influx of Na+ was further associated with an increase in Na+,K+-ATPase activity. Moreover, this stimulation of Na+ influx and Na+,K+-ATPase activity by CSF-1 was sensitive to pertussis toxin. Finally, we demonstrate that CSF-1-induced proliferation is also a pertussis toxin-sensitive event. The present findings thus suggest: 1) that the CSF-1 receptor is linked to a pertussis toxin-sensitive G protein; and 2) that a pertussis toxin-sensitive G protein is involved in the induction of Na+ influx by CSF-1.