心脏肌钙蛋白I的磷酸化调控与心衰

Cardiac troponin I phosphorylation and heart failure

心脏肌钙蛋白I(cTnI)是心肌收缩/舒张的关键性调控蛋白。多种激酶调控的cTnI磷酸化通过改变心肌纤维性状影响心脏功能。生理条件下,PKA依赖的cTnISer23/24磷酸化与PKC依赖的Ser43/45磷酸化相互拮抗,相互制衡,共同调控心脏的功能。心衰时,动态平衡被打破,cTnI出现磷酸化紊乱,Ser23/24"磷酸化不足"而Ser43/45则"磷酸化过度",肌纤维性状改变,心脏功能受损。除了PKA和PKC,PKG、PKD和PAK3等激酶亦对cTnI的磷酸化起调控作用。本文就cTnI磷酸化调控的分子机制及其对心衰作用研究的最新进展进行综述。

Cardiac troponin I (cTnI) is a key regulatory protein involved in cardiac muscle contraction and relaxation. Phosphorylation of specific serine and threonine residues on cTnI by several different kinases has profound effects on modulation of myofilament properties and cardiac function. Under physiological conditions, the cardiac contractile function achieves optimal performance by PKA-dependent Ser23/24 phosphorylation and PKC-dependent Ser43/45 phosphorylation. In pathological states, this fine balance is ...