The dual role of endothelial differentiation-related factor-1 in the cytosol and nucleus: Modulation by protein kinase A

E. Ballabio, M. Mariotti, L. De Benedictis, J. A M Maier

Research output: Contribution to journalArticlepeer-review

Abstract

Endothelial differentiation-related factor (EDF)-1 is involved in the repression of endothelial cell differentiation and is the first studied calmodulin (CaM)-binding protein in endothelial cells. Here we report that (i) EDF-1 is in vitro and in vivo phosphorylated by protein kinase A (PKA); (ii) EDF-1/CaM interaction is modulated by the phosphorylation of EDF-1 by PKA; (iii) forskolin stimulates nuclear accumulation of EDF-1, and (iv) PKA phosphorylation enhances EDF-1 interaction with the TATA-binding protein. CaM modulates the activity of several enzymes, among which is nitric oxide synthase (NOS). EDF-1, but not phosphorylated EDF-1, inhibits the activity of NOS. Accordingly, we detected an increase in NOS activity in cells that express low amounts of EDF-1. Our results indicate that EDF-1 serves two main functions in endothelial cells: (i) it regulates CaM availability in the cytosol, and (ii) it acts in the nucleus as a transcriptional coactivator.

Original languageEnglish
Pages (from-to)1069-1074
Number of pages6
JournalCellular and Molecular Life Sciences
Volume61
Issue number9
DOIs
Publication statusPublished - May 2004

Keywords

  • Differentiation
  • EDF-1/MBF-1
  • Endothelium

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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