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Ca(2+)-dependent gene expression mediated by MEF2 transcription factors
1Department of Pediatrics, Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
The Journal of Biological Chemistry
|January 5, 2000
Summary
Calcium signaling activates gene expression in T lymphocytes through MEF2 transcription factors. This process involves calcineurin and CaMKIV/Gr enzymes, highlighting a key pathway for immune cell activation.
Area of Science:
- Molecular Biology
- Immunology
- Cell Signaling
Background:
- Calcium ions (Ca2+) induce specific genes in lymphocytes, including immediate-early genes.
- These Ca2+-responsive elements are recognized by the MEF2 family of transcription factors.
Purpose of the Study:
- To elucidate the mechanism by which Ca2+ activates MEF2 response elements in T lymphocytes.
- To identify the specific enzymes involved in this Ca2+-mediated gene induction pathway.
Main Methods:
- Investigated the role of Ca2+/calmodulin-dependent enzymes in T lymphocyte gene activation.
- Analyzed the synergistic action of calcineurin and CaMKIV/Gr on MEF2 transcription factors (MEF2A and MEF2D).
- Examined the NFAT-dependent mechanism of calcineurin and the independent activation by CaMKIV/Gr.
Main Results:
- Ca2+ activation of MEF2 elements in T cells is synergistically mediated by calcineurin and CaMKIV/Gr.
- Calcineurin enhances MEF2A and MEF2D activity via an NFAT-dependent pathway.
- CaMKIV/Gr selectively and independently activates MEF2D.
Conclusions:
- MEF2 proteins act as crucial effectors in a T lymphocyte gene induction pathway.
- This pathway integrates various Ca2+ signaling inputs.
- The identified mechanism may have broad implications across multiple tissue types.