Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Cell Signal. 2017 Sep;37:1-11. doi: 10.1016/j.cellsig.2017.05.012. Epub 2017 May 18.
Cellular signal transmission requires the dynamic formation of spatiotemporally controlled molecular interactions. At the cell surface information is received by receptor complexes and relayed through intracellular signaling platforms which organize the actions of functionally interacting signaling enzymes and substrates. The list of hormone or neurotransmitter pathways that utilize the ubiquitous cAMP-sensing protein kinase A (PKA) system is expansive. This requires that the specificity, duration, and intensity of PKA responses are spatially and temporally restricted. Hereby, scaffolding proteins take the center stage for ensuring proper signal transmission. They unite second messenger sensors, activators, effectors, and kinase substrates within cellular micro-domains to precisely control and route signal propagation. A-kinase anchoring proteins (AKAPs) organize such subcellular signalosomes by tethering the PKA holoenzyme to distinct cell compartments. AKAPs differ in their modular organization showing pathway specific arrangements of interaction motifs or domains. This enables the cell- and compartment- guided assembly of signalosomes with unique enzyme composition and function. The AKAP-mediated clustering of cAMP and other second messenger sensing and interacting signaling components along with functional successive enzymes facilitates the rapid and precise dissemination of incoming signals. This review article delineates examples for different means of PKA regulation and for snapshots of compartmentalized PKA signalosomes.
细胞信号转导需要动态形成时空控制的分子相互作用。在细胞表面，受体复合物接收信息，并通过细胞内信号转导平台进行传递，该平台组织功能相互作用的信号酶和底物的作用。利用普遍存在的 cAMP 感应蛋白激酶 A（PKA）系统的激素或神经递质途径的列表是广泛的。这要求 PKA 反应的特异性、持续时间和强度在空间和时间上受到限制。在这里，支架蛋白成为确保适当信号转导的主角。它们将第二信使传感器、激活剂、效应物和激酶底物结合在细胞微域内，以精确控制和引导信号传递。蛋白激酶 A 锚定蛋白（AKAP）通过将 PKA 全酶锚定到不同的细胞区室，组织这种细胞内信号转导复合物。AKAP 在其模块化组织中存在差异，显示出相互作用基序或结构域的特定途径排列。这使得细胞和区室引导的信号转导复合物具有独特的酶组成和功能。AKAP 介导的 cAMP 和其他第二信使感应和相互作用信号成分的聚集以及功能连续酶的聚集促进了传入信号的快速和精确传播。这篇综述文章阐述了 PKA 调节的不同方式的例子，以及区室化 PKA 信号转导复合物的快照。
