May Lauren T, Hill Stephen J
Institute of Cell Signalling, School of Biomedical Sciences, Medical School, The University of Nottingham, Nottingham NG7 2UH, UK.
Int J Biochem Cell Biol. 2008;40(10):2013-7. doi: 10.1016/j.biocel.2008.04.001. Epub 2008 Apr 6.
G protein-coupled receptors (GPCRs) are a major target in the drug discovery process. One important response that results from activation of a wide range of GPCRs is activation of the ERK signalling cascade. Given the abundance of both upstream activators and downstream targets of ERK1/2, the precise spatiotemporal control of ERK1/2 phosphorylation is crucial for maintaining the specificity of the physiological outcome. ERK activity is regulated via a number of mechanisms including compartmentalisation and scaffolding proteins. These scaffolding proteins can enhance the transduction of a specific signalling pathway by targeting pathway components to particular intracellular locations or signalling complexes. Recently, a number of fluorescent indicators of ERK1/2 phosphorylation have been developed that allow the regulation of this pathway to be investigated with greater spatiotemporal resolution than was previously possible. These fluorescent probes in conjunction with those for other signalling cascades should help unravel the spatiotemporal organisation of this pathway.
G蛋白偶联受体（GPCRs）是药物研发过程中的主要靶点。多种GPCRs激活所产生的一个重要反应是ERK信号级联的激活。鉴于ERK1/2的上游激活剂和下游靶点数量众多，ERK1/2磷酸化的精确时空控制对于维持生理结果的特异性至关重要。ERK活性通过多种机制进行调节，包括区室化和支架蛋白。这些支架蛋白可通过将信号通路成分靶向特定的细胞内位置或信号复合物来增强特定信号通路的转导。最近，已开发出多种ERK1/2磷酸化的荧光指示剂，使得该信号通路的调节能够以比以往更高的时空分辨率进行研究。这些荧光探针与其他信号级联的探针相结合，应有助于揭示该信号通路的时空组织。
