Selective Disruption of the AKAP Signaling Complexes

Selective Disruption of the AKAP Signaling Complexes
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DOI:
10.1007/978-1-4939-2537-7_11
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发表时间:
2015-01-01
期刊:
CAMP SIGNALING: METHODS AND PROTOCOLS
影响因子:
--
通讯作者:
Scott, John D.
Scott, John D.
中科院分区:
其他
文献类型:
--
作者:
Kennedy, Eileen J.;Scott, John D.

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第二信使cAMP的合成激活对细胞内调节的所有方面都至关重要的多种信号传导途径。蛋白激酶A(PKA)是cAMP反应的主要效应子。这种酶在何时何地被激活对PKA的细胞作用有着深远的影响。A-激酶转运蛋白(AKAP)通过协调PKA作用的空间和时间方面在这一过程中发挥关键作用。评估这些锚定信号事件的影响的流行方法是生化干扰PKA AKAP接口。因此,PKA锚定肽干扰剂是研究PKA局部作用的有用工具。本文概述了PKA亚型选择性破坏肽的发展,文件的细胞可溶性肽衍生物的优化,并介绍了替代细胞为基础的方法,询问其他方面的PKA AKAP接口。
Synthesis of the second messenger cAMP activates a variety of signaling pathways critical for all facets of intracellular regulation. Protein kinase A (PKA) is the major cAMP-responsive effector. Where and when this enzyme is activated has profound implications on the cellular role of PKA. A-Kinase Anchoring Proteins (AKAPs) play a critical role in this process by orchestrating spatial and temporal aspects of PKA action. A popular means of evaluating the impact of these anchored signaling events is to biochemically interfere with the PKA AKAP interface. Hence, peptide disruptors of PKA anchoring are valuable tools in the investigation of local PKA action. This article outlines the development of PKA isoform-selective disruptor peptides, documents the optimization of cell-soluble peptide derivatives, and introduces alternative cell-based approaches that interrogate other aspects of the PKA AKAP interface.