c-Src kinase is involved in the tyrosine phosphorylation and activity of SLC11A1 in differentiating macrophages.
c-Src kinase is involved in the tyrosine phosphorylation and activity of SLC11A1 in differentiating macrophages.
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DOI：
10.1371/journal.pone.0196230
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Radzioch D
中科院分区：
文献类型：
--
作者：
Xu YZ;Thuraisingam T;Kanagaratham C;Tao S;Radzioch D
研究表明，溶质载体家族 11 成员 1 (SLC11A1) 在巨噬细胞中高度糖基化和磷酸化。然而，SLC11A1 磷酸化的机制以及磷酸化对 SLC11A1 活性的影响仍然很大程度上未知。在这里，当表达 SLC11A1 的 U937 细胞被佛波醇肉豆蔻酸酯乙酸酯 (PMA) 分化为巨噬细胞时，观察到 SLC11A1 的酪氨酸磷酸化。 PP2（Src 家族激酶的选择性抑制剂）治疗几乎完全阻断 SLC11A1 的磷酸化。此外，我们发现 SLC11A1 是活性 c-Src 激酶的直接底物，并且 siRNA 介导的细胞 Src (c-Src) 表达敲低会导致酪氨酸磷酸化显着降低。我们发现 PMA 诱导 SLC11A1 与 c-Src 激酶相互作用。我们证明，SLC11A1 在酪氨酸 15 处被 Src 家族激酶磷酸化，这种类型的磷酸化是 SLC11A1 介导的 LPS 诱导的 NF-κB 激活和一氧化氮 (NO) 产生调节所必需的。我们的结果证明 c-Src 酪氨酸激酶在巨噬细胞中 SLC11A1 的磷酸化和激活中发挥重要作用。
Studies have demonstrated that the solute carrier family 11 member 1 (SLC11A1) is heavily glycosylated and phosphorylated in macrophages. However, the mechanisms of SLC11A1 phosphorylation, and the effects of phosphorylation on SLC11A1 activity remain largely unknown. Here, the tyrosine phosphorylation of SLC11A1 is observed in SLC11A1-expressing U937 cells when differentiated into macrophages by phorbol myristate acetate (PMA). The phosphorylation of SLC11A1 is almost completely blocked by treatment with PP2, a selective inhibitor of Src family kinases. Furthermore, we found that SLC11A1 is a direct substrate for active c-Src kinase and siRNA-mediated knockdown of cellular Src (c-Src) expression results in a significant decrease in tyrosine phosphorylation. We found that PMA induces the interaction of SLC11A1 with c-Src kinase. We demonstrated that SLC11A1 is phosphorylated by Src family kinases at tyrosine 15 and this type of phosphorylation is required for SLC11A1-mediated modulation of NF-κB activation and nitric oxide (NO) production induced by LPS. Our results demonstrate important roles for c-Src tyrosine kinase in phosphorylation and activation of SLC11A1 in macrophages.
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