Phosphorylation of PDE4A5 by MAPKAPK2 attenuates fibrin degradation via p75 signalling (Retracted article. See OCT, 2022)
Phosphorylation of PDE4A5 by MAPKAPK2 attenuates fibrin degradation via p75 signalling (Retracted article. See OCT, 2022)
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DOI：
10.1093/jb/mvz016
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发表时间：
2019-07-01
影响因子：
2.7
通讯作者：
Baillie, G. S.
中科院分区：
文献类型：
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作者：
Houslay, K. F.;Fertig, B. A.;Baillie, G. S.
磷酸二酯酶（PDEs）塑造局部cAMP梯度，以支持受体功能的特异性。这个过程的关键是PDEs在细胞内位置的高度明确的性质。PDE4A5是一种特异性降解cAMP的PDE亚型，已知与p75神经营养因子受体（p75NTR）相关，在那里它调节cAMP信号级联反应，调节肺细胞外基质重塑。在这里，我们绘制并验证了新的蛋白-蛋白相互作用位点，这些位点对PDE4A5-p75NTR复合物的形成很重要，并首次表明MAPKAPK2对PDE4A5的磷酸化增强了PDE4A5与p75NTR的相互作用，而这反过来又有助于减弱纤维蛋白降解。
Phosphodiesterases (PDEs) shape local cAMP gradients to underpin the specificity of receptor function. Key to this process is the highly defined nature of the intra-cellular location of PDEs in the cell. PDE4A5 is a PDE isoform that specifically degrades cAMP and is known to associate with the p75 neurotrophin receptor (p75NTR) where it modulates cAMP signalling cascades that regulate extracellular matrix remodelling in the lungs. Here we map and validate novel protein-protein interaction sites that are important for formation of the PDE4A5-p75NTR complex and show, for the first time, that phosphorylation of PDE4A5 by MAPKAPK2 enhances PDE4A5 interaction with p75NTR and that this, in turn, serves to attenuate fibrin degradation.