Calcineurin-GATA-6 pathway is involved in smooth muscle-specific transcription.
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.
Wada
Hiromichi
H
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Hasegawa
Koji
K
Morimoto
Tatsuya
T
Kakita
Tsuyoshi
T
Yanazume
Tetsuhiko
T
Abe
Mitsuru
M
Sasayama
Shigetake
S
D000199:Actins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D019703:Calcineurin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017074:Common Variable Immunodeficiency; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D050993:GATA6 Transcription Factor; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D000199:Actins; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; D019703:Calcineurin; D018995:Myosin Heavy Chains