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首页> 外文期刊>Cytokine >MAST CELL-RESTRICTED p70 STAT6 ISOFORM IS A PRODUCT OF SELECTIVE PROTEOLYSIS.
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MAST CELL-RESTRICTED p70 STAT6 ISOFORM IS A PRODUCT OF SELECTIVE PROTEOLYSIS.

机译：肥大细胞限制性p70 STAT6同种型是选择性蛋白水解的产物。

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Signal transducer and activator of transcription (Stat)-6 is the principle Stat protein activated by interleukin (IL)-4. We defined a role for IL-4 in mast cell homeostasis through inhibiting expression of Kit and F(c)epsilonRI, and by inducing mast cell apoptosis. These effects required Stat6 expression. A molecular mechanism by which Stat6 directs these inhibitory actions in BMMC was potentially elucidated by the discovery of a carboxyl-truncated Stat6 isoform. Expression of this 70kDa isoform was unique to cultured mast cells and mast cell lines. Furthermore, this isoform lacked a carboxyl-transactivation domain, suggesting that it might behave as a dominant negative isoform. To better understand this truncated Stat6, we characterized its origins. Using Western blotting and electrophoretic mobility shift assay analysis, we assessed BMMC p70 Stat6 expression using standard and enhanced protease inhibitor cocktails. These experiments demonstrated that p70 Stat6 is derived by proteolysis during sample preparation, and has no cellular correlate. While some Stat family members are known to exist as naturally occurring truncated forms, p70 Stat6 does not appear to be such a case. Instead, the very high concentrations of proteases released during mast cell lysis result in selective proteolysis of the full-length Stat6, with p70 being the major degradation product.
机译：信号转导和转录激活因子（Stat）-6是白介素（IL）-4激活的主要Stat蛋白。我们通过抑制Kit和F（c）epsilonRI的表达以及诱导肥大细胞凋亡来定义IL-4在肥大细胞稳态中的作用。这些作用需要Stat6表达。通过发现羧基截短的Stat6同工型，可能阐明了Stat6指导BMMC中这些抑制作用的分子机制。该70kDa同工型的表达对于培养的肥大细胞和肥大细胞系是独特的。此外，该同工型缺乏羧基反式激活结构域，表明它可能表现为显性负性同工型。为了更好地理解此截断的Stat6，我们对它的起源进行了表征。使用蛋白质印迹和电泳迁移率变动分析，我们使用标准和增强的蛋白酶抑制剂混合物评估了BMMC p70 Stat6表达。这些实验表明，p70 Stat6是通过样品制备过程中的蛋白水解作用衍生出来的，与细胞没有任何相关性。虽然已知某些Stat家族成员以自然存在的截短形式存在，但p70 Stat6似乎不是这种情况。相反，在肥大细胞裂解期间释放的非常高浓度的蛋白酶会导致全长Stat6的选择性蛋白水解，其中p70是主要降解产物。

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