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和脂肪酸诱导膜子域内的c-Src聚类,导致JNK激活
Ryan G Holzer1, Eek-Joong Park, Ning Li
1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|October 4, 2011
概括
和脂肪酸激活Jun N-终端激酶 (JNK) 并通过改变c-Src蛋白分布来破坏胰岛素信号传递. 不和脂肪酸阻止了这种情况,为它们对葡萄糖代谢的有益作用提供了一个潜在的机制.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 代谢疾病 代谢疾病
背景情况:
- 和脂肪酸 (FA) 与胰岛素抵抗和2型糖尿病有关.
- 和FA的Jun N-终端激酶 (JNK) 激活与肥胖和胰岛素抵抗有关.
- 在细胞信号传输中,和的与不和的FA区分的机制尚不清楚.
研究的目的:
- 为了阐明和脂肪酸和不和脂肪酸是如何通过细胞信号通路进行歧视的.
- 研究c-Src激活在和FA对胰岛素信号传递的影响中介作用.
- 确定FA对JNK激活的差异效应背后的分子机制.
主要方法:
- 研究了和和不和FA对脂肪细胞中c-Src膜分布和激活的影响.
- 评估了FA诱导的c-Src激活对JNK信号和胰岛素信号通路的影响.
- 利用基基化抑制来确定其在FA介导的c-Src和JNK激活中的作用.
主要成果:
- 和的FA,但不是不和的FA,促进c-Src分裂成细胞内膜子域,导致其激活.
- 激活的c-Src调解JNK的激活,并通过和的FA抑制胰岛素信号传递.
- 不和的FA阻止c-Src膜的分割和激活,从而阻断JNK的激活.
- c-Src的基化对其膜分割和随后通过和FA的激活至关重要.
- 一种高脂肪饮食诱导了c-Src在小鼠脂肪细胞中的分割和激活.
结论:
- 和和不和FA之间的细胞区分涉及c-Src膜分布和激活的调节.
- 和的FA通过c-Src通路促进胰岛素抵抗和JNK激活.
- 不和的FA通过阻止c-Src激活和下游信号传递来产生保护作用.
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