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Updated: Jan 21, 2026

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通过非传统的三级接触,SH3域选择性地激活PI3激酶
Safia S Aljedani1,2,3, Anandsukeerthi Sandholu1, Abdullah Aldehaiman1
1Biological and Environmental Science and Engineering Division, KAUST Center of Excellence in Smart Health (KCSH), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Communications biology
|January 19, 2026
概括
特定的Src同质性3 (SH3) 域通过结合p85亚单元来激活氨酸-3激酶 (PI3K). 这项研究揭示了SH3域通过三级相互作用激活PI3K,而不仅仅是结合强度,确保选择性癌症路径控制.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 酸-3激酶 (PI3K) 途径对细胞代谢和生存至关重要.
- PI3K失调与癌症和其他疾病有关.
- 调节p85的子单元抑制催化p110的子单元.
研究的目的:
- 阐明Src同样性3 (SH3) 域激活PI3K的机制.
- 了解SH3域如何实现选择性PI3K激活,尽管其内在的特异性较低.
- 调查三级相互作用在SH3介导PI3K调节中的作用.
主要方法:
- 结构生物学技术 结构生物学技术
- 生物物理测定试验
- 功能性细胞检测试验
主要成果:
- 激活PI3K的SH3域与p85的C端域进行三级相互作用,缓解p110的抑制.
- 缺乏这些三级接触的SH3域与p85结合,具有相似的亲和力,但不激活PI3K.
- 对于PI3K激活,p85子单元使用一种依赖结合模式的选择机制,而不仅仅是结合亲和力.
结论:
- 该p85子单元赋予功能选择性,否则散乱的SH3域.
- 这种机制可以防止非特异性的PI3K激活.
- 为预测,调节和准SH3驱动PI3K激活在癌症等疾病中提供了一个框架.
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