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

doi:10.1083/jcb.200106057

Published online 11 March 2002. doi:10.1083/jcb.200106057

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© The Rockefeller University Press, 0021-9525/2002/3/983 $5.00
The Journal of Cell Biology, Volume 156, Number 6, March 18, 2002 983-991

Article

Calcineurin-GATA-6 pathway is involved in smooth muscle–specific transcription

Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto, Tsuyoshi Kakita, Tetsuhiko Yanazume, Mitsuru Abe and Shigetake Sasayama

Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan

Address correspondence to Koji Hasegawa, Dept. of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Tel.: 81-75-751-3190. Fax: 81-75-751-3203. E-mail: koj{at}kuhp.kyoto-u.ac.jp

Intracellular calcium is one of the important signals that initiatesthe myogenic program. The calcium-activated phosphatase calcineurinis necessary for the nuclear import of the nuclear factor ofactivated T cell (NFAT) family members, which interact withzinc finger GATA transcription factors. Whereas GATA-6 playsa role in the maintenance of the differentiated phenotype invascular smooth muscle cells (VSMCs), it is unknown whetherthe calcineurin pathway is associated with GATA-6 and playsa role in the differentiation of VSMCs. The smooth muscle–myosinheavy 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 NFATc1interacted with GATA-6. Consistent with this, NFATc1 furtherpotentiated GATA-6–activated Sm-MHC transcription. Inductionof VSMCs to the quiescent phenotype caused nuclear translocationof NFATc1. In differentiated VSMCs, blockage of calcineurindown-regulated the amount of GATA-6-DNA binding as well as theexpression of Sm-MHC and its transcriptional activity. Thesefindings demonstrate that the calcineurin pathway is associatedwith GATA-6 and is required for the maintenance of the differentiatedphenotype in VSMCs.

Key Words: smooth muscle; myosin; transcription; calcineurin; GATA-6

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