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Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 9, pp 1069–1074 | Cite as

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 Article

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.

Endothelium EDF-1/MBF-1 differentiation 

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Copyright information

© Birkhäuser-Verlag Basel 2004

Authors and Affiliations

  • E. Ballabio
    • 2
  • M. Mariotti
    • 1
  • L. De Benedictis
    • 1
  • J. A. M. Maier
    • 1
  1. 1.Department of Preclinical Sciences LITA VialbaUniversity of MilanMilanoItaly
  2. 2.DIBIT-H San RaffaeleMilanItaly

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