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Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2004 Dec; Vol. 18 (15), pp. 1909-11. Date of Electronic Publication: 2004 Sep 22. - Publication Year :
- 2004
-
Abstract
- We report here that apelin (65-77) activates p70 S6 kinase (p70S6K), not only in CHO cells that have been stably transfected with the apelin receptor, but also in umbilical endothelial cells (HUVEC), which express it endogenously. Apelin (65-77) induces a time-dependent phosphorylation of p70S6K at residues T421/S424 and T389. This dual phosphorylation is associated with two transduction cascades, involving a PI3K pathway and an ERK pathway, respectively. The PI3K pathway, which can be blocked by wortmannin, leads to phosphorylation of Akt at residues T308 or S473, which then promotes the phosphorylation of p70S6K at T421/S424 and T389. The ERK pathway is blocked by PD 098059, a MEK inhibitor, and results in the phosphorylation of p70S6K at T421/S424. Phosphorylation both of Akt and p70S6K is abrogated by pretreatment with pertussis toxin (PTX) and an inhibitor of atypical PKCs. In addition, we demonstrate that apelin (65-77) also increases the enzymatic activity of p70S6K and that the effects of the previously mentioned inhibitors on the level of T389 phosphorylation correlate with their action on enzyme activity. Interestingly, the main findings were reproduced in umbilical endothelial cells and apelin (65-77) promoted thymidine incorporation into DNA of these cells, revealing that apelin is a new mitogenic peptide for the endothelial cell.
- Subjects :
- Animals
CHO Cells
Cricetinae
Cricetulus
Endothelial Cells drug effects
Endothelial Cells enzymology
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors
Flavonoids pharmacology
Humans
Pertussis Toxin pharmacology
Phosphatidylinositol 3-Kinases metabolism
Phosphorylation
Protein Kinase C physiology
Protein Kinase Inhibitors pharmacology
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-akt
Signal Transduction
Sirolimus pharmacology
Umbilical Cord cytology
src-Family Kinases metabolism
Carrier Proteins pharmacology
Endothelium, Vascular enzymology
Mitogens pharmacology
Ribosomal Protein S6 Kinases, 70-kDa metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 18
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 15385434
- Full Text :
- https://doi.org/10.1096/fj.04-1930fje