Molecular mechanisms of feedback inhibition of protein kinase A on intracellular cAMP accumulation
- 作者：Jurgen Vandamme ; Dries Castermans ; Johan M. Thevelein ; johan.thevelein@mmbio.vib-kuleuven.be
- 关键词：cAMP-PKA pathway ; Feedback inhibition ; Adenylate cyclase ; Phosphodiesterase ; AKAP ; Saccharomyces cerevisiae ; Mammalian cells
- 刊名：Cellular Signalling
- 出版年：2012
- 期刊代码：42_08986568
- 类别：bio
- 出版时间：August, 2012
- 卷：24
- 期：8
- 页码：1610-1618
- 文件大小：638 K
摘要
The cAMP-protein kinase A (PKA) pathway is a major signalling pathway in the yeast Saccharomyces cerevisiae, but also in many other eukaryotic cell types, including mammalian cells. Since cAMP plays a crucial role as second messenger in the regulation of this pathway, its levels are strictly controlled, both in the basal condition and after induction by agonists. A major factor in the down-regulation of the cAMP level after stimulation is PKA itself. Activation of PKA triggers feedback down-regulation of the increased cAMP level, stimulating its return to the basal concentration. This is accomplished at different levels. The best documented mechanisms are: inhibition of cAMP synthesis by down-regulation of adenylate cyclase and/or its regulatory proteins, stimulation of cAMP breakdown by phosphodiesterases and spatial regulation of cAMP levels in the cell by A-Kinase Anchoring Proteins (AKAPs). In this review we describe these processes in detail for S. cerevisiae, for cells of mammals and selected other organisms, and we hint at other possible targets for feedback regulation of intracellular cAMP levels.