应力路径输出被依赖pH的酶组分的聚类编码
Yuliia Didan1, Milad Ghomlaghi2,3, Lan K Nguyen2,3
1School of Biomedical Science, Faculty of Medicine, University of Queensland; St Lucia, Brisbane, Australia.
Nature communications
|August 5, 2024
概括
细胞内pH (pHi) 显著影响c-Jun N-终端激酶 (JNK) 信号网络. 这项研究揭示了pHi如何调节JNK活动,影响细胞对压力的反应和潜在的癌症发展.
科学领域:
- 蜂信号传输是如何进行的
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 细胞内激酶调节生物过程,但它们在不断变化的细胞环境中的功能演变尚不清楚.
- c-Jun N-终端酶 (JNK) 信号的特异性受信号强度的影响.
研究的目的:
- 研究细胞内pH (pHi) 在JNK信号网络中的作用.
- 了解pHi如何调节JNK活动,以应对细胞压力和特定刺激.
- 探索pHi对JNK通路动态的影响及其对癌症生物学的影响.
主要方法:
- 利用光遗传集群标签CRY2诱导ASK1和JNK2的相变.
- 测量了对不同pHi水平和特定刺激的反应中的JNK活性.
- 运用数学建模来模拟反信号,包括pHi和ASK1/JNK2贡献.
主要成果:
- 细胞内pH值 (pHi) 是JNK网络的关键组成部分,定义信号反应.
- 增加的pHi增强了光诱导的ASK1相位过渡,增加了JNK激活.
- 增加的pHi促进了JNK2凝聚物的形成,但减弱了JNK的活动.
- 数学建模成功地根据pHi和ASK1/JNK2贡献划出了基于pHi和ASK1/JNK2贡献的特定信号反应.
结论:
- 在应对细胞压力和刺激时,pHi动态调节JNK信号传递.
- 对于信号特异性来说,pHi对ASK1和JNK2活动的差异性影响至关重要.
- 考虑pHi和ASK1/JNK2的贡献可以帮助区分致癌和瘤抑制的JNK功能,并告知癌症药物反应.
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