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Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species

机译:PDGF诱导的活性氧对Akt的亚型特异性调节

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摘要

Isoform-specific signaling of Akt, a major signaling hub and a prominent therapeutic target, remained poorly defined until recently. Subcellular distribution, tissue-specific expression, substrate specificity, and posttranslational modifications are believed to underlie isoform-specific signaling of Akt. The studies reported here show inhibition of Akt2 activity under physiologically relevant conditions of oxidation created by PDGF-induced reactive oxygen species. Combined MS and functional assays identified Cys124 located in the linker region between the N-terminal pleckstrin homology domain and the catalytic kinase domain as one of the unique regulatory redox sites in Akt2 with functional consequence on PDGF-stimulated glucose uptake. A model is proposed describing the consequence of increased endogenous oxidation induced by extracellular cues such as PDGF on Akt2 activity.
机译:直到最近,Akt的同工型特异性信号传导(主要的信号传导枢纽和重要的治疗靶点)仍不清楚。相信亚细胞分布,组织特异性表达,底物特异性和翻译后修饰是Akt的亚型特异性信号传导的基础。此处报道的研究表明,在PDGF诱导的活性氧产生的生理相关氧化条件下,Akt2活性受到抑制。结合的MS和功能测定确定Cys124位于N末端pleckstrin同源结构域和催化激酶结构域之间的接头区域是Akt2中独特的调节氧化还原位点之一,对PDGF刺激的葡萄糖摄取具有功能性影响。提出了一个模型,描述了由细胞外线索(例如PDGF)对Akt2活性引起的内源性氧化增加的后果。

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  • 作者单位

    Section on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine,Winston-Salem, NC 27109;

    Section on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine,Winston-Salem, NC 27109;

    Section on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine,Winston-Salem, NC 27109;

    Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109;

    Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109;

    Section on Molecular Medicine,Department of Biochemistry, Wake Forest University School of Medicine,Winston-Salem, NC 27109;

    Department of Mechanical and Information Engineering, University of Seoul, Seoul 130-743, Korea;

    Section on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine,Winston-Salem, NC 27109;

    Section on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine,Winston-Salem, NC 27109;

  • 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

    disulfide; receptor tyrosine kinase; DCF; DCP-Biol;

    机译:二硫化物受体酪氨酸激酶DCF;DCP生物;

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