Mg2+ as activator of uridine phosphorylation in coordination with other cellular responses to growth factors.
Mg2+ as activator of uridine phosphorylation in coordination with other cellular responses to growth factors.
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Mg2 作为尿苷磷酸化的激活剂，与其他细胞对生长因子的反应相协调。
DOI：
10.1073/pnas.0409082102
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Rubin,Harry
中科院分区：
文献类型：
--
作者：
Vidair,Charles;Rubin,Harry
二价阳离子离子载体A23187促进细胞内Mg 2+的操纵，而不增加细胞的一般渗透性。细胞对尿苷的摄取受到细胞内磷酸化速率的限制，细胞内磷酸化速率在加入生长因子后几分钟内增加。在这里描述的实验中，尿苷摄取率在离子载体处理的细胞刺激的血清或胰岛素依赖于细胞外和细胞内的Mg 2+浓度，是独立的细胞外Ca 2+浓度。在非常高浓度的Mg2+（50 mM），离子载体处理的细胞采取尿苷一样快，在生长因子的存在下，在不存在，表明Mg2+可以取代生长因子的需求，刺激尿苷摄取。与此相反，胸苷的摄取，这也是有限的细胞内磷酸化的速率，显示没有早期响应的生长因子或Mg2+浓度，这是一致的10倍低Mg2+的需要相比，尿苷激酶的胸苷激酶。尿苷激酶的反馈抑制UTP和CTP的无细胞提取物中的Mg2+浓度增加减轻。结果支持的论点，增加尿苷在细胞中的摄取与生长因子处理的细胞是由膜诱导的细胞内游离Mg2+增加。这种增加也会加速免疫起始和其他协调反应的速率，这与尿苷摄取增加不同，是细胞增殖所必需的。尿苷摄取率被认为是游离胞质Mg2+的直接指标，其驱动从静止到增殖的转变。
The divalent cation ionophore A23187 facilitates the manipulation of intracellular Mg2+without increasing the general permeability of the cell. The uptake of uridine into cells is limited by its rate of intracellular phosphorylation that increases within minutes after the addition of growth factors. In the experiments described here, the rate of uridine uptake in ionophore-treated cells stimulated by either serum or insulin depended on the extracellular and intracellular concentrations of Mg2+and was independent of the extracellular Ca2+concentration. In very high concentrations of Mg2+(50 mM), ionophore-treated cells take up uridine as fast, in the absence of growth factors as in their presence, demonstrating that Mg2+can replace the growth factor requirement for the stimulation of uridine uptake. In contrast, thymidine uptake, which also is limited by its rate of intracellular phosphorylation, showed no early response to either growth factors or Mg2+concentration, which is consistent with the 10-fold lower Mg2+requirement of thymidine kinase compared with uridine kinase. The feedback inhibition of uridine kinase by UTP and CTP in cell-free extracts was alleviated by increased Mg2+concentration. The results support the thesis that the increased uptake of uridine in cells treated with growth factors is determined by a membrane-induced increase in intracellular free Mg2+. Such increase would also accelerate the rate of translation-initiation and other coordinate responses that, unlike increased uridine uptake, are essential for cell proliferation. The rate of uridine uptake is suggested as a direct indicator of free cytosolic Mg2+that drives the shift from quiescence to proliferation.