Bauman Andrea L, Soughayer Joseph, Nguyen Bao T, Willoughby Debbie, Carnegie Graeme K, Wong Wei, Hoshi Naoto, Langeberg Lorene K, Cooper Dermot M F, Dessauer Carmen W, Scott John D
Howard Hughes Medical Institute, Vollum Institute, L-474, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.
Mol Cell. 2006 Sep 15;23(6):925-31. doi: 10.1016/j.molcel.2006.07.025.
Spatiotemporal organization of cAMP signaling begins with the tight control of second messenger synthesis. In response to agonist stimulation of G protein-coupled receptors, membrane-associated adenylyl cyclases (ACs) generate cAMP that diffuses throughout the cell. The availability of cAMP activates various intracellular effectors, including protein kinase A (PKA). Specificity in PKA action is achieved by the localization of the enzyme near its substrates through association with A-kinase anchoring proteins (AKAPs). Here, we provide evidence for interactions between AKAP79/150 and ACV and ACVI. PKA anchoring facilitates the preferential phosphorylation of AC to inhibit cAMP synthesis. Real-time cellular imaging experiments show that PKA anchoring with the cAMP synthesis machinery ensures rapid termination of cAMP signaling upon activation of the kinase. This protein configuration permits the formation of a negative feedback loop that temporally regulates cAMP production.
环磷酸腺苷（cAMP）信号传导的时空组织始于对第二信使合成的严格控制。响应于G蛋白偶联受体的激动剂刺激，膜相关腺苷酸环化酶（AC）产生cAMP，其在整个细胞中扩散。cAMP的可用性激活各种细胞内效应器，包括蛋白激酶A（PKA）。PKA作用的特异性是通过该酶通过与A激酶锚定蛋白（AKAP）结合而定位在其底物附近来实现的。在这里，我们提供了AKAP79/150与ACV和ACVI之间相互作用的证据。PKA锚定促进AC的优先磷酸化以抑制cAMP合成。实时细胞成像实验表明，PKA与cAMP合成机制的锚定可确保激酶激活后cAMP信号的快速终止。这种蛋白质构型允许形成负反馈回路，从而在时间上调节cAMP的产生。
