Parnell Euan, Smith Brian O, Yarwood Stephen J
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ, UK.
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ, UK.
Cell Signal. 2015 May;27(5):989-96. doi: 10.1016/j.cellsig.2015.02.009. Epub 2015 Feb 12.
We have identified a conserved nuclear pore localisation signal (NPLS; amino acids 764-838 of EPAC1) in the catalytic domains of the cAMP-sensors, EPAC1 and EPAC2A. Consequently, EPAC1 is mainly localised to the nuclear pore complex in HEK293T cells where it becomes activated following stimulation with cAMP. In contrast, structural models indicate that the cAMP-binding domain of EPAC2A (CNBD1) blocks access to the conserved NPLS in EPAC2A, reducing its ability to interact with nuclear binding sites. Consequently, a naturally occurring EPAC2 isoform, EPAC2B, which lacks CNBD1 is enriched in nuclear fractions, similar to EPAC1. Structural differences in EPAC isoforms may therefore determine their intracellular location and their response to elevations in intracellular cAMP.
我们在环磷酸腺苷（cAMP）传感器EPAC1和EPAC2A的催化结构域中鉴定出一个保守的核孔定位信号（NPLS；EPAC1的第764 - 838位氨基酸）。因此，EPAC1主要定位于HEK293T细胞的核孔复合体，在受到cAMP刺激后被激活。相比之下，结构模型表明EPAC2A的cAMP结合结构域（CNBD1）会阻碍对EPAC2A中保守NPLS的接近，从而降低其与核结合位点相互作用的能力。因此，一种天然存在的缺乏CNBD1的EPAC2亚型EPAC2B在核组分中富集，类似于EPAC1。因此，EPAC亚型的结构差异可能决定它们在细胞内的位置以及对细胞内cAMP升高的反应。
Zotero 插件
