Delineation of type I protein kinase A-selective signaling events using an RI anchoring disruptor
Delineation of type I protein kinase A-selective signaling events using an RI anchoring disruptor
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DOI：
10.1074/jbc.m603223200
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发表时间：
2006-07-28
影响因子：
4.8
通讯作者：
Scott, John D.
中科院分区：
文献类型：
--
作者：
Carlson, Cathrine Rein;Lygren, Birgitte;Scott, John D.
cAMP信号的特异性控制是通过A激酶锚定蛋白（AKAPs）实现的，它将cAMP效应物如蛋白激酶A （PKA）组装成细胞内的多蛋白信号复合物。akap将PKA全酶拴在亚细胞位置，有利于选定底物的磷酸化。PKA锚定是由每个AKAP上14-18个残基的两亲螺旋介导的，该螺旋与PKA全酶的R亚基二聚体结合。结合生物信息学和肽阵列筛选，我们开发了一种名为RIAD （RI锚定干扰物）的高亲和结合肽，它对I型PKA的选择性是II型PKA的1000倍。细胞可溶性RIAD选择性地解除camp介导的T细胞功能抑制，并抑制类固醇生成细胞线粒体的孕酮合成。这项研究表明，这些过程是由I型PKA全酶控制的，RIAD可以作为一种工具来定义锚定的I型PKA信号事件。
Control of specificity in cAMP signaling is achieved by A-kinase anchoring proteins (AKAPs), which assemble cAMP effectors such as protein kinase A (PKA) into multiprotein signaling complexes in the cell. AKAPs tether the PKA holoenzymes at subcellular locations to favor the phosphorylation of selected substrates. PKA anchoring is mediated by an amphipathic helix of 14-18 residues on each AKAP that binds to the R subunit dimer of the PKA holoenzymes. Using a combination of bioinformatics and peptide array screening, we have developed a high affinity-binding peptide called RIAD ( RI anchoring disruptor) with > 1000-fold selectivity for type I PKA over type II PKA. Cell-soluble RIAD selectively uncouples cAMP-mediated inhibition of T cell function and inhibits progesterone synthesis at the mitochondria in steroid-producing cells. This study suggests that these processes are controlled by the type I PKA holoenzyme and that RIAD can be used as a tool to define anchored type I PKA signaling events.