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Publication : Calcineurin-GATA-6 pathway is involved in smooth muscle-specific transcription.

First Author  Wada H Year  2002
Journal  J Cell Biol Volume  156
Issue  6 Pages  983-91
PubMed ID  11889139 Mgi Jnum  J:168211
Mgi Id  MGI:4887344 Doi  10.1083/jcb.200106057
Citation  Wada H, et al. (2002) Calcineurin-GATA-6 pathway is involved in smooth muscle-specific transcription. J Cell Biol 156(6):983-91
abstractText  Intracellular calcium is one of the important signals that initiates the myogenic program. The calcium-activated phosphatase calcineurin is necessary for the nuclear import of the nuclear factor of activated T cell (NFAT) family members, which interact with zinc finger GATA transcription factors. Whereas GATA-6 plays a role in the maintenance of the differentiated phenotype in vascular smooth muscle cells (VSMCs), it is unknown whether the calcineurin pathway is associated with GATA-6 and plays a role in the differentiation of VSMCs. The smooth muscle-myosin heavy chain (Sm-MHC) gene is a downstream target of GATA-6, and provides a highly specific marker for differentiated VSMCs. Using immunoprecipitation Western blotting, we showed that NFATc1 interacted with GATA-6. Consistent with this, NFATc1 further potentiated GATA-6-activated Sm-MHC transcription. Induction of VSMCs to the quiescent phenotype caused nuclear translocation of NFATc1. In differentiated VSMCs, blockage of calcineurin down-regulated the amount of GATA-6-DNA binding as well as the expression of Sm-MHC and its transcriptional activity. These findings demonstrate that the calcineurin pathway is associated with GATA-6 and is required for the maintenance of the differentiated phenotype in VSMCs.
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