模拟磷酸化依赖性相互作用与 14-3-3 蛋白介导的细胞信号通讯。

Modelling cellular signal communication mediated by phosphorylation dependent interaction with 14-3-3 proteins.

机构信息

Division for Psychiatry, Haukeland University Hospital, Sandviksleitet 1, 5036 Bergen, Norway; K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.

K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.

出版信息

FEBS Lett. 2014 Jan 3;588(1):92-8. doi: 10.1016/j.febslet.2013.11.012. Epub 2013 Nov 20.

DOI:10.1016/j.febslet.2013.11.012

PMID:24269229

Abstract

The 14-3-3 proteins are important effectors of Ser/Thr phosphorylation in eukaryotic cells. Using mathematical modelling we investigated the roles of these proteins as effectors in signalling pathways that involve multi-phosphorylation events. We defined optimal conditions for positive and negative cross-talk. Particularly, synergistic signal interaction was evident at very different sets of binding affinities and phosphorylation kinetics. We identified three classes of 14-3-3 targets that all have two binding sites, but displayed synergistic interaction between converging signalling pathways for different ranges of parameter values. Consequently, these protein targets will respond differently to interventions that affect 14-3-3 binding affinities or phosphorylation kinetics.

摘要

14-3-3 蛋白是真核细胞中 Ser/Thr 磷酸化的重要效应物。我们使用数学建模研究了这些蛋白作为涉及多磷酸化事件的信号通路中的效应物的作用。我们定义了正、负串扰的最佳条件。特别是，在非常不同的结合亲和力和磷酸化动力学集上，协同信号相互作用是明显的。我们确定了具有两个结合位点的 14-3-3 靶标的三个类别，但对于不同的参数值范围，汇聚信号通路之间的协同相互作用。因此，这些蛋白靶标对影响 14-3-3 结合亲和力或磷酸化动力学的干预会有不同的反应。