GATA-5 is involved in leukemia inhibitory factor-responsive transcription of the β-myosin heavy chain gene in cardiac myocytes

Tatsuya Morimoto, Koji Hasegawa, Satoshi Kaburagi, Tsuyoshi Kakita, Hiroshi Masutani, Richard N. Kitsis, Akira Matsumori, Shigetake Sasayama

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Abstract

Leukemia inhibitory factor is a member of a family of structurally related cytokines sharing the receptor component gp130. Activation of gp130 by leukemia inhibitory factor is sufficient to induce myocardial cell hypertrophy accompanied by specific changes in the pattern of gene expression. However, the molecular mechanisms that link gp130 activation to these changes have not been clarified. The present study investigated the transcriptional pathways by which leukemia inhibitory factor activates β- myosin heavy chain expression during myocardial cell hypertrophy. Mutation of the GATA motif in the β-myosin heavy chain promoter totally abolished leukemia inhibitory factor-responsive transcription without changing basal transcriptional activity. In contrast, endothelin-1 responsiveness was unaffected by the GATA mutation. Among members of the cardiac GATA transcription factor subfamily (GATA-4, -5, and -6), GATA-5 was the sole and potent transactivator for the β-myosin heavy chain promoter. This transactivation was dependent on sequence-specific binding of GATA-5 to the β-myosin heavy chain GATA element. Cardiac nuclear factors that bind to to the β-myosin heavy chain GATA element were induced by leukemia inhibitory factor stimulation. Last, leukemia inhibitory factor stimulation markedly increased transcripts of cardiac GATA-5, the expression of which is normally restricted to the early embryo. Thus, GATA-5 may be involved in gp130 signaling in cardiac myocytes.

Original languageEnglish (US)
Pages (from-to)12811-12818
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number18
DOIs
Publication statusPublished - Apr 30 1999

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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