Kopperud Reidun, Krakstad Camilla, Selheim Frode, Døskeland Stein Ove
Department of Anatomy and Cell Biology, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
FEBS Lett. 2003 Jul 3;546(1):121-6. doi: 10.1016/s0014-5793(03)00563-5.
Cyclic AMP (cAMP) has traditionally been thought to act exclusively through cAMP-dependent protein kinase (cAPK, PKA), but a growing number of cAMP effects are not attributable to general activation of cAPK. At present, cAMP is known also to directly regulate ion channels and the ubiquitous Rap guanine exchange factors Epac 1 and 2. Adding to the sophistication of cAMP signaling is the fact that (1) the cAPK holoenzyme is incompletely dissociated even at saturating cAMP, the level of free R subunit of cAPK being able to regulate the maximal activity of cAPK, (2) cAPK activity can be modulated by oxidative glutathionylation, and (3) cAPK is anchored close to relevant substrates, other signaling enzymes, and local compartments of cAMP. Finally, we will demonstrate an example of fine-tuning of cAMP signaling through synergistic induction of neurite extensions by cAPK and Epac.
传统上认为环磷酸腺苷（cAMP）仅通过依赖于cAMP的蛋白激酶（cAPK，PKA）发挥作用，但越来越多的cAMP效应不能归因于cAPK的全面激活。目前已知cAMP还可直接调节离子通道以及普遍存在的Rap鸟嘌呤交换因子Epac 1和Epac 2。使cAMP信号传导更为复杂的是以下事实：（1）即使在cAMP饱和时，cAPK全酶也不能完全解离，cAPK游离R亚基的水平能够调节cAPK的最大活性；（2）cAPK活性可通过氧化谷胱甘肽化作用进行调节；（3）cAPK锚定在相关底物、其他信号酶以及cAMP的局部区域附近。最后，我们将展示一个通过cAPK和Epac协同诱导神经突延伸来微调cAMP信号传导的例子。
