Premium
Characterization of a Novel Cardiac Isoform of the Cell Cycle‐related Kinase
Author(s) -
Qiu Hongyu,
Shen YouTang,
Vatner Dorothy E.,
Vatner Stephen F.,
Depre Christophe
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.588.1
Subject(s) - cell cycle , biology , alternative splicing , gene isoform , kinase , casein kinase 1 , microbiology and biotechnology , cyclin , cyclin dependent kinase 1 , protein kinase a , cell , gene , biochemistry
We examined a genomic profile in monkey hearts subjected to myocardial infarction (MI) followed by pacing‐induced heart failure (HF), to identify novel mechanisms involved in the pathogenesis of HF. One candidate was the transcript encoding the cell cycle‐related kinase (CCRK), which decreased by 50% in HF (P<0.05). The CCRK sequence cloned from the heart showed the same N‐terminal kinase domain as the “generic” isoform cloned previously, but a different C‐terminal half due to alternative splicing with frame shift. Expression of the protein, confirmed by monoclonal antibody, was limited to heart, liver and kidney. Upon overexpression in cardiac myocytes, both the generic and cardiac isoforms promoted cell growth and decreased apoptosis (P<0.05 vs control). The “generic” but not the cardiac CCRK interacted with cyclin H and casein kinase 2 in a yeast two‐hybrid, phosphorylated the cyclin‐dependent kinase 2, and increased the number of myocytes in the S and G2 phases of the cell cycle (P<0.05 vs control). Therefore, the heart expresses a variant of CCRK, which promotes cardiac cell growth and survival similarly to the “generic” form, but both isoforms differ in terms of protein‐protein interactions, substrate specificity and re‐entry in the cell cycle. Antagonizing the down‐regulation of CCRK expression in the transition to HF could protect the heart and enhance regeneration of failing myocardium.