Gerits Nancy, Kostenko Sergiy, Shiryaev Alexey, Johannessen Mona, Moens Ugo
Department of Microbiology and Virology, University of Tromsø, N-9037 Tromsø, Norway.
Cell Signal. 2008 Sep;20(9):1592-607. doi: 10.1016/j.cellsig.2008.02.022. Epub 2008 Mar 14.
Inter- and intracellular communications and responses to environmental changes are pivotal for the orchestrated and harmonious operation of multi-cellular organisms. These well-tuned functions in living organisms are mediated by the action of signal transduction pathways, which are responsible for receiving a signal, transmitting and amplifying it, and eliciting the appropriate cellular responses. Mammalian cells posses numerous signal transduction pathways that, rather than acting in solitude, interconnect with each other, a phenomenon referred to as cross-talk. This allows cells to regulate the distribution, duration, intensity and specificity of the response. The cAMP/cAMP-dependent protein kinase (PKA) pathway and the mitogen-activated protein kinase (MAPK) cascades modulate common processes in the cell and multiple levels of cross-talk between these signalling pathways have been described. The first- and best-characterized interconnections are the PKA-dependent inhibition of the MAPKs ERK1/2 mediated by RAF-1, and PKA-induced activation of ERK1/2 interceded through B-RAF. Recently, novel interactions between components of these pathways and new mechanisms for cross-talk have been elucidated. This review discusses both known and novel interactions between compounds of the cAMP/PKA and MAPKs signalling pathways in mammalian cells.
细胞间和细胞内通讯以及对环境变化的反应对于多细胞生物的协调和谐运作至关重要。生物体中这些协调良好的功能由信号转导通路介导，信号转导通路负责接收信号、传递和放大信号，并引发适当的细胞反应。哺乳动物细胞拥有众多信号转导通路，这些通路并非孤立作用，而是相互连接，这种现象称为串扰。这使细胞能够调节反应的分布、持续时间、强度和特异性。环磷酸腺苷/环磷酸腺苷依赖性蛋白激酶（PKA）通路和丝裂原活化蛋白激酶（MAPK）级联反应调节细胞中的常见过程，并且已经描述了这些信号通路之间多个层面的串扰。最先被发现且研究最充分的相互连接是由RAF-1介导的PKA对MAPK ERK1/2的依赖性抑制作用，以及由B-RAF介导的PKA诱导的ERK1/2激活。最近，这些通路的组成成分之间的新型相互作用以及串扰的新机制已被阐明。本综述讨论了哺乳动物细胞中环磷酸腺苷/PKA和MAPK信号通路化合物之间已知和新型的相互作用。
