Cardiac troponin I phosphorylation and heart failure
WANG Xiao-jian,HUI Ru-tai,Key Laboratory of Clinical Cardiovascular Genetics, Ministry of Education (Sino-German Laboratory for Molecular Medicine), Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China;
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 disrupted. The Ser23/24 is "hypo-phosphorylation" whereas the Ser43/45 is "hyper-phosphorylaed". The alternations in cTnI phosphorylation may contribute to impaired contractile function. Besides PKA and PKC, cTnI may also be specifically modified by PKD, PKG and PAK3. This review summarized recent advances in understanding the mechanisms of cTnI modification and the consequent functional effects both under physiological conditions and in heart failure.