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.
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. Maier. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-682X. - 61:9(2004), pp. 1069-1074.
The dual role of endothelial differentiation-related factor-1 in the cytosol and nucleus: modulation by protein kinase A
M. Mariotti;J.A. Maier
2004
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.Pubblicazioni consigliate
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