Subcellular Organization of the cAMP Signaling Pathway,Pharmacological Reviews

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Subcellular Organization of the cAMP Signaling Pathway
Pharmacological Reviews ( IF 19.3 ) Pub Date : 2021-01-01 , DOI: 10.1124/pharmrev.120.000086
Manuela Zaccolo ₁ , Anna Zerio ₂ , Miguel J Lobo ₂

Affiliation

The field of cAMP signaling is witnessing exciting developments with the recognition that cAMP is compartmentalized and that spatial regulation of cAMP is critical for faithful signal coding. This realization has changed our understanding of cAMP signaling from a model in which cAMP connects a receptor at the plasma membrane to an intracellular effector in a linear pathway to a model in which cAMP signals propagate within a complex network of alternative branches and the specific functional outcome strictly depends on local regulation of cAMP levels and on selective activation of a limited number of branches within the network. In this review, we cover some of the early studies and summarize more recent evidence supporting the model of compartmentalized cAMP signaling, and we discuss how this knowledge is starting to provide original mechanistic insight into cell physiology and a novel framework for the identification of disease mechanisms that potentially opens new avenues for therapeutic interventions.

中文翻译：

cAMP 信号通路的亚细胞组织

cAMP 信号传导领域正在见证令人兴奋的发展，人们认识到 cAMP 是区分开的，并且 cAMP 的空间调节对于忠实的信号编码至关重要。这一认识改变了我们对 cAMP 信号传导的理解，从 cAMP 将质膜上的受体以线性途径连接到细胞内效应器的模型，转变为 cAMP 信号在替代分支和特定功能结果的复杂网络中传播的模型严格依赖于 cAMP 水平的局部调节以及网络内有限数量分支的选择性激活。在这篇综述中，我们介绍了一些早期研究，并总结了支持区室化 cAMP 信号传导模型的最新证据，并讨论了这些知识如何开始为细胞生理学提供原始的机制见解以及识别疾病机制的新框架这可能为治疗干预开辟新的途径。

更新日期：2020-12-18

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