【bio-news】CARDIAC RYANODINE RECEPTOR PHOSPHORYLATION:TARG
A study by Xiao and co-workers in this issue of the Biochemical Journal demonstrates PKA (protein kinase A)-dependent phosphorylation of Ser-2030 on the cardiac ryanodine receptor (RyR2) that is activated by β-adrenergic agonists. They show that RyR2 phosphorylation at this site is not appreciably altered in heart failure samples, but retains PKA-dependence of phosphorylation. They contrast this with RyR2 phosphorylation at Ser-2808, a site previously reported to be the key and only PKAtarget site on RyR2. Here Ser-2808 phosphorylation was found to be relatively insensitive to either PKA activation or inhibition. These results add important new information to a highly controversial field. This issue is important because it is increasingly clear that altered regulation of the gating of the RyR2 sarcoplasmic reticulum Ca2+- release channel (e.g. by phosphorylation) is critically important in mediating altered diastolic sarcoplasmic reticulum Ca2+ release. This may contribute to both reduced cardiac function and arrhythmogenesis in humans carrying mutations in the RyR2 gene and with acquired heart failure of varied aetiology. This study brings some new answers, but also raises additional new questions that will require further investigation.
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在这期《生化》杂志中XIAO与其合作者进行的一项研究证实由B型肾上腺素能激动剂激活的心脏RYANODINE受体（RYR2）的Ser-2030的磷酸化是依赖于PKA。他们证实在心力衰竭模型中这一位点的RYR2磷酸化有明显的改变，但PKA依赖的磷酸化却不变。他们将其同RYR2的Ser-2808磷酸化进行比较，Ser-2808是先前已经报道的PKA作用于RYR2上唯一的关键靶点。此处，发现Ser-2808的磷酸化对PKA的激活或抑制相对不敏感。这些发现给争论激烈的领域增添了新的信息。这一结果很重要，因为肌浆网钙离子释放通道RYR2闸门的调节改变（如磷酸化）在介导舒张期肌浆网钙离子释放时很关键这一点逐渐明确。这一点使携带有RYR2突变基因的人易产生心功能减退和心律失常发生，且是导致后天性心力衰竭的各种病因。这个研究不但给出了一些新的答案，而且提出了新问题并需要进一步的研究。
关于心肌组织上 ryanodine receptor (RyR2)的一些介绍:
RYR2也是一种大分子复合物，包括蛋白激酶A，磷酸酶(PP1 and PP2a)，藤霉素结合蛋白12.6 , 钙调蛋白，钙离子/钙调蛋白依赖蛋白激酶2，磷酸二酯酶4D，triadin 和junctin ，以上成分都参与调节RyR2门控通道。它是心肌细胞兴奋收缩耦联时,心肌细胞浆内钙离子浓度急剧增高所必需的,即钙离子释放的主要的离子通道.
A study by Xiao and co-workers in this issue of the Biochemical Journal demonstrates PKA (protein kinase A)-dependent phosphorylation of Ser-2030 on the cardiac ryanodine receptor (RyR2) that is activated by β-adrenergic agonists.
在这期《生化》杂志中XIAO与其合作者进行的一项研究证实由B型肾上腺素能激动剂激活的心脏RYANODINE受体（RYR2）的Ser-2030的磷酸化是依赖于PKA。
我认为应该是：在这期《生化》杂志中XIAO与其合作者进行的一项研究证实：心脏RYANODINE受体（RYR2）上Ser-2030的依赖于PKA磷酸化是由B型肾上腺素能激动剂激活的。
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作者:admin@医学,生命科学 2011-02-16 17:14
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