Abstract
Ca2+/calmodulin-dependent protein kinase II (CaMKII) and calcineurin (CaN) are positive regulators of cardiac hypertrophy, but the nature of cross-talk between CaMKII and CaN signaling pathways in hypertrophic cardiomyocytes remains unclear. Here we documented that CaMKIIδ3 activation enhances transcription of the CaN gene through activation of the CaN-Aβ subunit (CnAβ) promoter in rat cultured cardiomyocytes. Co-immunoprecipitation assays showed that MEF2 forms a complex with GATA4 following transfection of an active CaMKIIδ3 (T278D) mutant in neonatal cardiomyocytes. Inversely, transfection of a dominant negative CaMKIIδ3 mutant failed to promote a MEF2-GATA4 complex. Consistent with these observations, immunocytochemistry indicated nuclear co-localization of MEF2 with GATA4 after hypertrophic agonist stimulation or CaMKIIδ3 (T278D) transfection. These data demonstrate that CaMKII can enhance CnAβ promoter activity by enhancing MEF2-GATA4 synergy, suggesting a novel mechanism for CaMKII-mediated hypertrophic signaling, which contributes to induction and development of the hypertrophic response through CaN activation.
Original language | English |
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Pages (from-to) | 429-441 |
Number of pages | 13 |
Journal | Biochimica et Biophysica Acta - Gene Regulatory Mechanisms |
Volume | 1799 |
Issue number | 5-6 |
DOIs | |
Publication status | Published - 2010 |
Keywords
- CaMKII
- Calcineurin
- GATA4
- Hypertrophy
- MEF2c
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics