Bone morphogenetic protein-2 inhibits MAPK-dependent Elk-1 transactivation and DNA synthesis induced by EGF in mesangial cells

Goutam Ghosh Choudhury, Dong Chan Jin, Yong Soo Kim, Anthony Celeste, Nandini Ghosh-Choudhury, Hanna E. Abboud

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Bone morphogenetic protein-2 (BMP-2) is a member of the TGFβ superfamily of growth and differentiation factors. We investigated the effect of BMP-2 on epidermal growth factor (EGF)-induced mitogenic signaling in kidney glomerular mesangial cells. BMP-2 dose-dependently inhibits EGF-induced DNA synthesis. Maximum effect was obtained at a concentration of 100 ng/ml. BMP-2 had no inhibitory effect on the EGF receptor (EGFR)-associated tyrosine kinase activity indicating that inhibition of DNA synthesis is due to regulation of post-receptor signaling event(s). EGF stimulates MAPK activity in mesangial cells in a time-dependent manner. Inhibition of MAPK by the MEK inhibitor PD098059 blocks EGF-induced DNA synthesis indicating the requirement of this enzyme activity in EGF-mediated mitogenic signaling. Furthermore, we show that exposure of mesangial cells to BMP-2 blocks EGF-induced MAPK activity which leads to phosphorylattion of Elk-1 transcription factor. Using a GAL-4 DNA binding-domain-Elk-1 transactivation domain fusion protein-based reporter assay, we demonstrate that BMP-2 inhibits EGF-induced Elk-1-mediated transcription. These data provide the first evidence that BMP-2 signaling in mesangial cells initiates a negative regulatory cross-talk with MAPK-based transcription to inhibit EGF-induced DNA synthesis.

Original languageEnglish (US)
Pages (from-to)490-496
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume258
Issue number2
DOIs
StatePublished - May 10 1999

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Bone morphogenetic protein-2 inhibits MAPK-dependent Elk-1 transactivation and DNA synthesis induced by EGF in mesangial cells'. Together they form a unique fingerprint.

Cite this