摘要
提出了一个计算机模型,利用该模型对表皮生长因子(EGF)激活的ERK信号转导网络进行了综合量化和动力学模拟.数学模型包含了各个途径的激活动力学,多条反馈回路和构架蛋白的连接.并对EGF受体和激活其下游的级联蛋白提出了新的认识.通过分析ERK信号转导途径正负反馈回路对信号转导的影响,发现这些反馈回路是ERK信号转导网络振荡的主要影响因素,它们能够导致下游底物的表达和相应的细胞行为.
Extra-cellular signal regulated kinase （ERK） signal network plays an important role in regulating the fundamental cellular functions such as cell proliferation, survival, differentiation, and motility. Development and analysis of mathematical model can help us acquire a deep understanding of the complex behavior of ERK signal transduction network. This paper presents a computational model that offers an integrated quantitative and dynamic simulation of ERK signal Wansduction network, activated by epidermal growth factor （EGF）. The mathematic model contains the activation kinetics of the pathway, a multitude of feedback loops and connection of scaffold proteins. The model pro- vides the insights into signal-response relationships between the binding of EGF to its receptor at the cell surface and activation of downstream proteins in the signaling cascade. The different influence of positive and negative feedback loops of the ERK signal transduction pathway were mainly analyzed, indicating that feedback loops were the main impacting factor to the oscillation of ERK signal transduction pathway. The predictions of this oscillation of ERK activation agree well with the literature. It can lead to signal waves of the downstream substrates and induce corresponding biological behaviors.
出处
《分子科学学报》
CAS
CSCD
北大核心
2009年第4期260-267,共8页
Journal of Molecular Science
基金
国家自然科学基金资助项目(10801025)
大连理工大学青年教师培养基金资助项目(1000-893231)
大连理工大学博士科研启动基金资助项目(1000-893361)
关键词
ERK
反馈回路
振荡
ERK
feedback loops
oscillation
