时娜
中国医学科学院阜外医院 内分泌中心
The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 2013
Myocyte's contraction is regulated by signal transduction pathway composed with many protein factors, but the definite mechanism is still uncertain. A novel cardiac-specific kinase gene which participates in regulation of signal transduction, p93 named, was cloned from adult heart cDNA library. p93, coding a family member of MAPKKK, localized on 1p31.1 based on bioinformatics analyses. Northern blot and 76-tissue array analyses determined that p93 was merely expressed in heart, but was undetectable in other tissues. Immunohistochemical study showed that p93 predominantly localized in the nucleus of cardiac myocytes. In vitro kinase assay indicated that p93 was a functional kinase capable of autophosphorylation. p93 could directly interact with cardiac troponin I by yeast two-hybrid system assessed utilizing bait plasmid containing p93 C-terminus (733 835 aa) and results were further confirmed by co-immunoprecipitation in vivo. Our data suggest that p93 is a cardiac-specific kinase and may play important role in regulation of sarcomeric contraction protein with signal transduction pathway similar ILK.
Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica 2003
