Sands William A, Palmer Timothy M
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK.
Cell Signal. 2008 Mar;20(3):460-6. doi: 10.1016/j.cellsig.2007.10.005. Epub 2007 Oct 12.
Many of the effects of prototypical second messenger cyclic adenosine 3',5'-monophosphate (cAMP) on complex processes such as the regulation of fuel metabolism, spermatogenesis and steroidogenesis are mediated via changes in target gene transcription. A large body of research has defined members of the cAMP-response element binding (CREB) protein family as the principal mediators of positive changes in gene expression in response to cAMP following phosphorylation by cAMP-dependent protein kinase (PKA). However, persistent observations of cAMP-mediated induction of specific genes occurring via PKA-independent mechanisms have challenged the generality of the PKA-CREB pathway. In this review, we will discuss in detail both PKA-dependent and -independent mechanisms that have been proposed to explain how cAMP influences the activation status of multiple transcription factors, and how these influence critical biological processes whose defective regulation may lead to disease.
典型的第二信使3',5'-环磷酸腺苷（cAMP）对诸如燃料代谢调节、精子发生和类固醇生成等复杂过程的许多影响是通过靶基因转录的变化介导的。大量研究已将环磷酸腺苷反应元件结合（CREB）蛋白家族成员定义为在被环磷酸腺苷依赖性蛋白激酶（PKA）磷酸化后，响应cAMP时基因表达正向变化的主要介导因子。然而，持续观察到cAMP通过不依赖PKA的机制诱导特定基因，这对PKA-CREB途径的普遍性提出了挑战。在本综述中，我们将详细讨论已提出的依赖PKA和不依赖PKA的机制，这些机制解释了cAMP如何影响多种转录因子的激活状态，以及这些转录因子如何影响关键的生物学过程，其调节缺陷可能导致疾病。
