p90RSK2,一种新的MLCK调节了肌肉光链激酶无光滑肌肉中的收缩性
Jaspreet Kalra1, Mykhaylo Artamonov1,2, Hua Wang1,3
1Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, United States.
Frontiers in physiology
|October 2, 2023
概括
在平滑肌肉收缩过程中,p90核糖体S6激酶 (RSK2) 补偿了肌轻链激酶1 (MLCK1) 的缺失. RSK2形成了一个信号复合体,以酸化髓素光链,揭示了一条调节血管度的新途径.
科学领域:
- 分子生物学分子生物学
- 身体生理学 身体生理学
- 生物化学 生化学
背景情况:
- 滑动肌肉 (SM) 收缩受肌肉酶调节光链 (RLC20) 酸化的调节.
- 氨酸轻链激酶1 (MLCK1) 传统上被认为是负责这种酸化的唯一激酶.
- 新出现的证据表明,辅助激酶有助于血管SM调和收缩性.
研究的目的:
- 研究p90核糖体S6激酶 (RSK2) 在没有MLCK1.1的情况下平滑肌肉收缩性中的补偿作用.
- 阐明RSK2调节RLC20酸化和平滑肌肉收缩的信号通路.
- 为了确定RSK2是否作为平滑肌肉中RLC20酸化的替代激酶.
主要方法:
- 使用了MLCK1无 (mylk1-/-) 小鼠胚胎光滑肌肉组织 (E14.5-18.5).
- 评估了对激动剂的反应中的光滑肌肉收缩性和RLC20酸化.
- 采用RSK2抑制,GTPγS刺激,卡利库林A治疗以及近距离结合/免疫沉测试.
- 研究了Ca2+依赖型氨酸激酶Pyk2在RSK2介导信号传递中的作用.
主要成果:
- 在mylk1-/-光滑肌中,激素诱导的收缩和RLC20酸化被RSK2抑制减弱.
- 虽然Ca2+敏感度保持不变,但在mylk1-/-肌肉中,力响应的大小减少了.
- RSK2,PDK1,ERK1/2和MLCK在乙烯丝上形成了一个信号复合体,促进了RLC20酸化.
- 这两种Ca2+依赖 (通过Pyk2/PDK1/RSK2) 和Ca2+独立 (通过Erk1/2/PDK1/RSK2) 途径都对RLC20的酸化和收缩有所贡献.
结论:
- RSK2信号传递是平滑肌肉收缩中MLCK1的重要补偿途径.
- RSK2与其他激酶和活性蛋白一起形成一个功能信号复合体,直接化RLC20.
- 这项研究确定了一种新的第三途径 (RSK2信号传递),与Ca2+/CaM/MLCK和RhoA/ROCK途径一起调节光滑肌肉收缩性.
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