Brown Matthew D, Sacks David B
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States.
Cell Signal. 2009 Apr;21(4):462-9. doi: 10.1016/j.cellsig.2008.11.013. Epub 2008 Dec 3.
The mitogen-activated protein kinase (MAPK) pathway allows cells to interpret external signals and respond in an appropriate way. Diverse cellular functions, ranging from differentiation and proliferation to migration and inflammation, are regulated by MAPK signalling. Therefore, cells have developed mechanisms by which this single pathway modulates numerous cellular responses from a wide range of activating factors. This specificity is achieved by several mechanisms, including temporal and spatial control of MAPK signalling components. Key to this control are protein scaffolds, which are multidomain proteins that interact with components of the MAPK cascade in order to assemble signalling complexes. Studies conducted on different scaffolds, in different biological systems, have shown that scaffolds exert substantial control over MAPK signalling, influencing the signal intensity, time course and, importantly, the cellular responses. Protein scaffolds, therefore, are integral elements to the modulation of the MAPK network in fundamental physiological processes.
丝裂原活化蛋白激酶(MAPK)信号通路使细胞能够解读外部信号并以适当方式做出反应。从分化、增殖到迁移和炎症等多种细胞功能均受MAPK信号传导调控。因此,细胞已形成相关机制,通过这一单一信号通路调节来自多种激活因子的众多细胞反应。这种特异性通过多种机制实现,包括对MAPK信号成分的时空控制。这种控制的关键是蛋白质支架,它是多结构域蛋白,与MAPK级联反应的成分相互作用以组装信号复合物。在不同生物系统中对不同支架进行的研究表明,支架对MAPK信号传导有实质性控制作用,影响信号强度、时间进程,重要的是,还影响细胞反应。因此,蛋白质支架是基础生理过程中MAPK网络调节的不可或缺的元件。