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使用向质谱和动态建模阐明纤维细胞生长因子诱导的基因组动力学

Tim S Veth¹, Chiara Francavilla², Albert J R Heck¹

¹Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, The Netherlands; Netherlands Proteomics Center, Utrecht, The Netherlands.

Molecular & cellular proteomics : MCP

|June 16, 2023

概括

纤维细胞生长因子 (FGFs) 触发不同的细胞反应. 这项研究绘制了激酶活性动态图,揭示了连体特异性通路,并确定了参与FGF信号传递的新型激酶,这对于了解细胞生长和癌症进展至关重要.

科学领域:

细胞生物学细胞生物学
分子信号传输的方法
生物化学生物化学

背景情况:

纤维细胞生长因子 (FGFs) 是关键的信号蛋白调节重要的细胞过程,如增殖和上皮细胞转移到介质细胞.
控制FGF介导的细胞反应的精确分子动力学仍然不完全理解.
阐明这些途径对于理解正常生理和疾病状态,包括癌症至关重要.

研究的目的:

为了研究FGF受体激活下游的依赖联体激酶活性动态.
为了识别参与FGF信号通路的新激酶.
为了建模和验证针对特定的FGF配体的基因组动态.

主要方法:

用各种FGF连接体 (FGF2,FGF3,FGF4,FGF10,FGF19) 刺激了MCF-7乳腺癌细胞.
44种激酶的激酶活性用向质谱学量化.
全系统的激酶活性数据与 () 蛋白质组学数据进行了整合,以进行综合分析.
使用基于逻辑的动态建模来分析基因组动态.

主要成果:

通过不同FGFs的刺激,显现出明显的,依赖于连接体的通路动态.
该研究发现了以前未报告的激酶参与,包括MARK.
激酶活性数据和建模精确定位了FGF2的BRAF驱动激活和FGF4.4的ARAF驱动激活.

结论:

FGF信号表现出复杂的,对联体特定的通路激活配置文件.
这些发现扩大了参与FGF反应的已知基因组,并完善了对途径效应的理解.
动态建模为验证信号通路的生物模型提供了一个强大的框架.

关键词:

乳腺癌乳腺癌乳腺癌纤维母细胞细胞是如何形成的增长因素增长因素基诺姆基诺姆 (Kinome Kinome) 是一个类型的基因组.这就是MAPKK的意思.建模建模模型是什么酸蛋白组学酸蛋白组学酸蛋白组学在SRM中,我们可以使用SRM.信号传输信号传输有针对性的成员国.

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