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Multiple phosphorylation sites on the RegA phosphodiesterase regulate Dictyostelium development

机译:Rega磷酸二酯酶的多个磷酸化位点调节Dictyostelium开发

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In Dictyostelium, the intracellular cAMP-specific phosphodiesterase RegA is a negative regulator of cAMP-dependent protein kinase (PICA), a key determinant in the timing of developmental morphogenesis and spore formation. To assess the role of protein kinases in the regulation of RegA function, this study identified phosphorylation sites on RegA and characterized the role of these modifications through the analysis of phosphomimetic and phospho-ablative mutations. Mutations affecting residue T676 of RegA, a presumed target of the atypical MAP kinase Erk2, altered the rate of development and impacted cell distribution in chimeric organisms suggesting that phosphorylation of this residue reduces RegA function and regulates cell localization during multicellular development. Mutations affecting the residue S142 of RegA also impacted the rate developmental morphogenesis but in a manner opposite of changes at T676 suggesting the phosphorylation of the S142 residue increases RegA function. Mutations affecting residue S413 residue altered aggregate sizes and delayed developmental progression suggesting that PKA operates in a negative feedback mechanism to increase RegA function. These results suggest that the phosphorylation of different residues on RegA can lead to increased or decreased RegA function and therefore in turn regulate developmental processes such as aggregate formation, cell distribution, and the kinetics of developmental morphogenesis.
机译:在Dictyostelium中,细胞内阵营特异性磷酸二酯酶Rega是营养依赖性蛋白激酶(PICA)的负调节剂,是发育形态发生和孢子形成时的关键决定因素。为了评估蛋白激酶在Rega功能调节中的作用,该研究确定了Rega上的磷酸化位点,并通过分析磷酸磷和磷烧蚀突变来表征这些修饰的作用。影响Rega残留物T676的突变是非典型地图激酶ERK2的假定靶,改变了嵌合生物中的发育速率和受影响的细胞分布,表明该残余物的磷酸化降低了多细胞发育过程中的细胞定位。影响Rega残基S142的突变也影响了速率发育形态发生,但以与T676的变化相反的方式表明S142残基的磷酸化增加了Rega功能。影响残余物S413残基的突变改变了总尺寸和延迟发育进展,表明PKA在负反馈机制中运行以增加Rega功能。这些结果表明,Rega上不同残留物的磷酸化可以导致Rega功能的增加或降低,因此调节群体形成,细胞分布和发育形态发生的动力学。

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