Mayor Federico, Jurado-Pueyo Maria, Campos Pedro M, Murga Cristina
Departamento de Biología Molecular, and Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, Spain.
Cell Cycle. 2007 Mar 1;6(5):528-33. doi: 10.4161/cc.6.5.3920. Epub 2007 Mar 25.
Docking interactions are key to understand the dynamic assembly of signal transduction complexes in the cell. In particular, the docking domain (D domain)-dependent interactions described so far for several MAPK routes are essential to specify the upstream regulators, downstream mediators and also inactivators that complex with the p38, JNK and ERK proteins. In addition to contributing to the maintenance of the linearity and specificity of these pathways, novel data have revealed that docking contacts also regulate the activity, subcellular distribution and substrate selection of each MAPK. Moreover, phosphorylation inside or around a docking domain is emerging as a novel mechanism of regulation of MAPK association with cellular partners, suggesting new potential strategies for the design of selective MAPK inhibitors. Here, we discuss these novel data and the biochemical and cellular implications they may have with specific emphasis on the p38 route.
对接相互作用是理解细胞中信号转导复合物动态组装的关键。特别是，目前已描述的几种丝裂原活化蛋白激酶（MAPK）途径中依赖对接结构域（D结构域）的相互作用对于确定与p38、JNK和ERK蛋白复合的上游调节因子、下游介质以及失活剂至关重要。除了有助于维持这些途径的线性和特异性外，新数据还表明对接接触也调节每个MAPK的活性、亚细胞分布和底物选择。此外，对接结构域内部或周围的磷酸化正成为调节MAPK与细胞伴侣结合的一种新机制，这为设计选择性MAPK抑制剂提出了新的潜在策略。在这里，我们讨论这些新数据及其可能具有的生化和细胞意义，并特别强调p38途径。
