Cell signaling pathways for the regulation of GATA4 transcription factor: Implications for cell growth and apoptosis.

GATA4 is a member of the GATA family of zinc finger transcription factor, which regulates gene transcription by binding to GATA elements. GATA4 was originally discovered as a regulator of cardiac development and subsequently identified as a major regulator of adult cardiac hypertrophy. GATA4 regulates gene expression of various genes, which are involved in cardiac development and cardiac hypertrophy and heart failure. In addition to the heart, GATA4 plays important roles in the reproductive system, gastrointestinal system, respiratory system and cancer. Positive and negative regulations of GATA4 therefore are important components of biologic functions. The activation of GATA4 occurs via various cell signaling events. Earlier studies have identified protein-protein interactions of GATA4 with other factors. The discovery of interactions of GATA4 with nuclear factor for activated T cells (NFAT) revealed the importance of calcium signaling in the activation of GATA4. GATA4 can also be phosphorylated by mitogen activated protein kinases and protein kinase A. Lysine modifications also occur on the GATA4 molecule including acetylation and sumoylation. Both reactive oxygen-dependent and -independent antioxidant-sensitive pathways for GATA4 activation have also been demonstrated. The GATA4 activity is also regulated by modulating the level of GATA4 expression via transcriptional as well as translational mechanisms. This work summarizes the current understanding of regulatory mechanisms for modulating GATA4 activity.