蛋白磷酸酶1与Ca^(2+)/钙调素依赖性蛋白激酶Ⅱ在心肌病中研究进展

Roles of protein phosphatase 1 and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in heart disease

蛋白质的磷酸化与去磷酸化是细胞信号转导过程中最重要的调控方式,其循环过程就像调控分子的开关一样,参与众多生理活动。负责这一修饰调节的是蛋白激酶与蛋白磷酸酶。报道显示人类染色体编码多达500个蛋白激酶,这些蛋白激酶满足人类高度多样性与差异性调控蛋白磷酸化作用,而有趣的是人类编码的蛋白磷酸酶却仅仅约为150个,其中约有40个是丝氨酸/苏氨酸蛋白磷酸酶。越来越多的证据表明蛋白磷酸酶/蛋白激酶调控异常在心肌病中起关键作用。蛋白磷酸酶1(protein phosphatase 1,PP1)是一多功能的丝氨酸/苏氨酸蛋白磷酸酶,研究显示PP1在心肌肥厚和心衰的发生发展过程中起重要作用。而Ca2+/钙调素依赖性蛋白激酶Ⅱ(Ca2+/calmodulin-dependent protein kinaseⅡ,CaMKⅡ)是一种多功能的丝氨酸/苏氨酸蛋白激酶,它作为Ca2+信号转导的关键因子,调节细胞的多种生物学功能,其功能异常可引起肥厚心肌胞内钙稳态失衡进而引起心律失常等心肌病。该文就PP1与CaMKⅡ的功能和心肌病的关系作一综述。

Phosphorylation and dephosphorylation of protein play an important role in the process of signal transduction,and its cycle,similar to the switching which regulates molecular,involves in many physiological activities.Protein kinases and protein phosphatases are a critical regulated pathway of phosphorylation and dephosphorylation of protein.Protein phosphatase 1（PP1） is a multifunctional protein phosphatase and plays an important role in pathogenesis of cardiac hypertrophy and heart failure.Ca^2＋/calmodulin-dependent protein kinase Ⅱ（CaMKⅡ） is also a multifunctional enzyme involved in the regulation of gene expression,cell cycle control,and differentiation.There is growing evidence for a pathophysiological role of CaMKⅡ in cardiac hypertrophy and heart failure.The article focuses on the progress in roles of PP1 and CaMKⅡ in cardiac physiology and pathophysiology.