Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".

IF 7.9 Q1 Medicine Wiley Interdisciplinary Reviews-Systems Biology and Medicine Pub Date : 2020-09-01 Epub Date: 2020-04-23 DOI:10.1002/wsbm.1490
Michael Getz, Padmini Rangamani, Pradipta Ghosh
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引用次数: 4

Abstract

A number of hormones and growth factors stimulate target cells via the second messenger pathways, which in turn regulate cellular phenotypes. Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that facilitates numerous signal transduction pathways; its production in cells is tightly balanced by ligand-stimulated receptors that activate adenylate cyclases (ACs), that is, "source" and by phosphodiesterases (PDEs) that hydrolyze it, that is, "sinks." Because it regulates various cellular functions, including cell growth and differentiation, gene transcription and protein expression, the cAMP signaling pathway has been exploited for the treatment of numerous human diseases. Reduction in cAMP is achieved by blocking "sources"; however, elevation in cAMP is achieved by either stimulating "source" or blocking "sinks." Here we discuss an alternative paradigm for the regulation of cellular cAMP via GIV/Girdin, the prototypical member of a family of modulators of trimeric GTPases, Guanine nucleotide Exchange Modulators (GEMs). Cells upregulate or downregulate cellular levels of GIV-GEM, which modulates cellular cAMP via spatiotemporal mechanisms distinct from the two most often targeted classes of cAMP modulators, "sources" and "sinks." A network-based compartmental model for the paradigm of GEM-facilitated cAMP signaling has recently revealed that GEMs such as GIV serve much like a "tunable valve" that cells may employ to finetune cellular levels of cAMP. Because dysregulated signaling via GIV and other GEMs has been implicated in multiple disease states, GEMs constitute a hitherto untapped class of targets that could be exploited for modulating aberrant cAMP signaling in disease states. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Biological Mechanisms > Cell Signaling.

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调节细胞环腺苷一磷酸:“源”,“汇”,现在是“可调阀”。
许多激素和生长因子通过第二信使途径刺激靶细胞,从而调节细胞表型。环腺苷一磷酸(cAMP)是一种普遍存在的第二信使,促进了许多信号转导途径;它在细胞中的产生是由激活腺苷酸环化酶(ACs)的配体刺激受体(即“源”)和水解它的磷酸二酯酶(PDEs)紧密平衡的,磷酸二酯酶(PDEs)是“源”。因为它调节各种细胞功能,包括细胞生长和分化、基因转录和蛋白质表达,cAMP信号通路已被用于治疗许多人类疾病。减少cAMP是通过阻断“来源”实现的;然而,cAMP的升高是通过刺激“源”或阻断“汇”来实现的。在这里,我们讨论了通过GIV/Girdin调节细胞cAMP的另一种范例,GIV/Girdin是三聚体GTPases调节家族的原型成员,鸟嘌呤核苷酸交换调节剂(GEMs)。细胞上调或下调GIV-GEM的细胞水平,其通过不同于两种最常见的cAMP调节剂(“源”和“汇”)的时空机制调节细胞cAMP。最近,一个基于网络的gem促进cAMP信号传导范例的区室模型揭示,诸如GIV之类的gem就像一个“可调阀”,细胞可以利用它来微调cAMP的细胞水平。由于通过GIV和其他GEMs的信号失调与多种疾病状态有关,GEMs构成了迄今为止尚未开发的一类靶标,可以用于调节疾病状态中的异常cAMP信号。本文分类如下:系统特性和过程模型>机制模型生物学机制>细胞信号传导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
18.40
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine Focus: Strong interdisciplinary focus Serves as an encyclopedic reference for systems biology research Conceptual Framework: Systems biology asserts the study of organisms as hierarchical systems or networks Individual biological components interact in complex ways within these systems Article Coverage: Discusses biology, methods, and models Spans systems from a few molecules to whole species Topical Coverage: Developmental Biology Physiology Biological Mechanisms Models of Systems, Properties, and Processes Laboratory Methods and Technologies Translational, Genomic, and Systems Medicine
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