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.
|Titolo:||The dual role of endothelial differentiation-related factor-1 in the cytosol and nucleus: modulation by protein kinase A|
|Autori interni:||MARIOTTI, MASSIMO|
MAIER, JEANETTE ANNE MARIE
|Parole Chiave:||Endothelium, EDF-1/MBF-1, differentiation|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2004|
|Digital Object Identifier (DOI):||10.1007/s00018-004-4016-0|
|Appare nelle tipologie:||01 - Articolo su periodico|
File in questo prodotto:
- PubMed Central loading...