Cross Talk between Signaling and Vitamin A Transport by the Retinol-Binding Protein Receptor STRA6
Cross Talk between Signaling and Vitamin A Transport by the Retinol-Binding Protein Receptor STRA6
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DOI：
10.1128/mcb.00505-12
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发表时间：
2012-08-01
影响因子：
5.3
通讯作者：
Noy, Noa
中科院分区：
文献类型：
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作者：
Berry, Daniel C.;O'Byrne, Sheila M.;Noy, Noa
质膜蛋白 STRA6 将维生素 A 从其血液载体视黄醇结合蛋白 (RBP) 转运到细胞中，并且它还充当激活 JAK/STAT 信号传导的细胞因子受体。我们在此表明，与其他细胞因子受体不同，STRA6 的磷酸化并不是简单地在其胞外配体结合时诱导的。相反，受体的激活是由 STRA6 介导的视黄醇从血清 RBP 易位至细胞内受体（视黄醇结合蛋白 CRBP-I）触发的。观察结果还表明，视黄醇从 RBP 到 CRBP-I 的移动以及由此激活的 STRA6 与维生素的细胞内代谢密切相关。此外，数据表明 STRA6 磷酸化是视黄醇摄取进行的必要条件。因此，观察结果表明，STRA6 精心策划了一个多组分“机器”，将维生素 A 稳态和代谢与信号级联的激活结合起来，反过来，STRA6 信号传导调节细胞对维生素的摄取。 STRA6 似乎是一类新蛋白质的创始成员，该蛋白质可被称为“细胞因子信号传导转运蛋白”。
The plasma membrane protein STRA6 transports vitamin A from its blood carrier retinol binding protein (RBP) into cells, and it also functions as a cytokine receptor which activates JAK/STAT signaling. We show here that, unlike other cytokine receptors, phosphorylation of STRA6 is not simply induced upon binding of its extracellular ligand. Instead, activation of the receptor is triggered by STRA6-mediated translocation of retinol from serum RBP to an intracellular acceptor, the retinol-binding protein CRBP-I. The observations also demonstrate that the movement of retinol from RBP to CRBP-I, and thus activation of STRA6, is critically linked to the intracellular metabolism of the vitamin. Furthermore, the data show that STRA6 phosphorylation is required for retinol uptake to proceed. Hence, the observations demonstrate that STRA6 orchestrates a multicomponent "machinery" that couples vitamin A homeostasis and metabolism to activation of a signaling cascade and that, in turn, STRA6 signaling regulates the cellular uptake of the vitamin. STRA6 appears to be a founding member of a new class of proteins that may be termed "cytokine signaling transporters."