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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses
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Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses

机译：维生素A和视黄醇结合蛋白的信号调节基因表达以抑制胰岛素反应

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摘要

It currently is believed that vitamin A, retinol, functions through active metabolites: the visual chromophore 11-cis-retinal, and ret-inoic acids, which regulate gene transcription. Retinol circulates in blood bound to retinol-binding protein (RBP) and is transported into cells by a membrane protein termed "stimulated by retinoic acid 6" (STRA6). We show here that STRA6 not only is a vitamin A transporter but also is a cell-surface signaling receptor activated by the RBP-retinol complex. Association of RBP-retinol with STRA6 triggers tyrosine phosphorylation, resulting in recruitment and activation of JAK2 and the transcription factor STAT5. The RBP-retinol/STRA6/JAK2/STAT5 signaling cascade induces the expression of STAT target genes, including suppressor of cytokine signaling 3 (SOCS3), which inhibits insulin signaling, and peroxisome proliferator-activated receptor gamma (PPARγ), which enhances lipid accumulation. These observations establish that the parental vitamin A molecule is a transcriptional regulator in its own right, reveal that the scope of biological functions of the vitamin is broader than previously suspected, and provide a rationale for understanding how RBP and retinol regulate energy homeostasis and insulin responses.
机译：目前认为，维生素A，视黄醇通过活性代谢物起作用：视觉发色团11-顺-视网膜和视黄酸，它们调节基因转录。视黄醇在与视黄醇结合蛋白（RBP）结合的血液中循环，并通过称为“由视黄酸6刺激”的膜蛋白（STRA6）转运到细胞中。我们在这里显示STRA6不仅是维生素A转运蛋白，而且是由RBP-视黄醇复合物激活的细胞表面信号受体。 RBP-视黄醇与STRA6的结合会触发酪氨酸磷酸化，从而导致JAK2和转录因子STAT5的募集和激活。 RBP-视黄醇/ STRA6 / JAK2 / STAT5信号传导级联诱导STAT目标基因的表达，包括抑制胰岛素信号传导的细胞因子信号传导抑制因子3（SOCS3）和过氧化物酶体增殖物激活受体γ（PPARγ），后者可增强脂质蓄积。 。这些观察结果证明，亲本维生素A分子本身就是转录调节剂，揭示了该维生素的生物学功能范围比以前所怀疑的要广，并为理解RBP和视黄醇如何调节能量稳态和胰岛素反应提供了理论依据。 。

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  • 作者

    Daniel C. Berry; Hui Jin; Avijit Majumdar; Noa Noy;

  • 作者单位

    Departments of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106;

    Departments of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106;

    Departments of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106;

    Departments of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    retinoids; adipokine; obesity; insulin-resistance;

    机译：类维生素A;脂肪因子肥胖;胰岛素抵抗;

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