Gα13 induces preproET-1 gene expression via JNK

Ken Yamakawa, Kenichiro Kitamura, Hiroshi Nonoguchi, Nobuyuki Takasu, R. Tyler Miller, Kimio Tomita

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The endothelin B receptor (ETBR) has been shown to mediate autoinduction of endothelin-1 (ET-1). We previously reported that the ETBR interacts with Gα13, a member of the heterotrimeric GTP-binding protein family. In the present study, we examined whether Gα13, induces preproET-1 (ppET-1) gene transcription, which could result in ET-1 autoinduction in a renal epithelial cell line. We generated a reporter gene construct under control of the ppET-1 promoter region. The construct was transiently expressed in COS-7 cells. Transient expression of ETBR increased the promoter activity of ppET-1 following treatment with 100 nmol/l of ET-1. Expression of Gα13Q226L or GαqQ209L, constitutively active forms of Gα13 and Gαq, also activated the ppET-1 promoter. ETBR-stimulated ppET-1 promoter activity was partially diminished by the expression of dominant negative forms of c-Jun N-terminal kinase (JNK1APF) or MAPK/ERK kinase (MEKK97M). Expression of JNK1APF also inhibited Gα13Q226L-induced ppET-1 promoter activation. These findings indicate that Gα13 can induce ppET-1 gene expression through a JNK-mediated pathway. Our results also suggest that this Gα13-coupled signaling pathway may play an important role in a sustained ET-1 autoinduction loop in various pathophysiological conditions.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalHypertension Research
Volume25
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Endothelin
  • Endothelin receptor
  • G-protein
  • Transcription

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Yamakawa, K., Kitamura, K., Nonoguchi, H., Takasu, N., Miller, R. T., & Tomita, K. (2002). Gα13 induces preproET-1 gene expression via JNK. Hypertension Research, 25(3), 427-432. https://doi.org/10.1291/hypres.25.427