ERK Signals: Scaffolding Scaffolds?
ERK Signals: Scaffolding Scaffolds?
复制标题
DOI：
10.3389/fcell.2016.00049
复制
发表时间：
2016
影响因子：
5.5
通讯作者：
Crespo P
中科院分区：
文献类型：
--
作者：
Casar B;Crespo P
ERK 1/2 MAP激酶通过由连续层细胞质激酶组成的信号传导模块响应于多种细胞内和细胞外刺激而被激活。支架蛋白通过将模块的不同组分连接成多酶复合物来调节ERK信号，通过该复合物来微调信号幅度和持续时间，并且还通过将该复合物与外部干扰隔离来提供信号保真度。此外，支架蛋白作为ERK信号的空间调节剂发挥核心作用。在这方面，根据激活信号发出的亚细胞定位，定义的支架指定哪些底物适合磷酸化。最近的证据揭示了不同支架蛋白种类之间的直接相互作用。这些支架-支架大复合物可以构成ERK信号的额外调节水平，并且可以作为传入信号的整合和随后传出信号相对于底物接合的多样化的节点。
ERK1/2 MAP Kinases become activated in response to multiple intra- and extra-cellular stimuli through a signaling module composed of sequential tiers of cytoplasmic kinases. Scaffold proteins regulate ERK signals by connecting the different components of the module into a multi-enzymatic complex by which signal amplitude and duration are fine-tuned, and also provide signal fidelity by isolating this complex from external interferences. In addition, scaffold proteins play a central role as spatial regulators of ERKs signals. In this respect, depending on the subcellular localization from which the activating signals emanate, defined scaffolds specify which substrates are amenable to be phosphorylated. Recent evidence has unveiled direct interactions among different scaffold protein species. These scaffold-scaffold macro-complexes could constitute an additional level of regulation for ERK signals and may serve as nodes for the integration of incoming signals and the subsequent diversification of the outgoing signals with respect to substrate engagement.