Small GTP-binding protein Ral is involved in cAMP-mediated release of von Willebrand factor from endothelial cells.
| Autor: | Rondaij MG; Department of Plasma Proteins, Sanquin Research at CLB, Amsterdam, The Netherlands. J.Voorberg@sanquin.nl, Sellink E, Gijzen KA, ten Klooster JP, Hordijk PL, van Mourik JA, Voorberg J |
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| Jazyk: | angličtina |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2004 Jul; Vol. 24 (7), pp. 1315-20. Date of Electronic Publication: 2004 May 06. |
| DOI: | 10.1161/01.ATV.0000131267.13425.45 |
| Abstrakt: | Objective: von Willebrand factor (vWF) is synthesized by endothelial cells and stored in specialized vesicles called Weibel-Palade bodies (WPBs). Recently, we have shown that the small GTP-binding protein Ral is involved in thrombin-induced exocytosis of WPBs. In addition to Ca2+-elevating secretagogues such as histamine and thrombin, release of WPB is also observed after administration of cAMP-raising substances such as epinephrine and vasopressin. In the present study, we investigated whether Ral is also involved in cAMP-mediated vWF release. Methods and Results: Activation of Ral was observed 15 to 20 minutes after stimulation of endothelial cells with epinephrine, forskolin, or dibutyryl-cAMP. A cell-permeable peptide comprising the carboxy-terminal part of the Ral protein reduced both thrombin-induced and epinephrine-induced vWF secretion supporting a crucial role for Ral in this process. Furthermore, inhibition of protein kinase A by H-89 resulted in a marked reduction of vWF release and greatly diminished levels of GTP-Ral on stimulation with epinephrine. Activation of Ral was independent of the activation of Epac, a cAMP-regulated exchange factor for the small GTPases Rap1 and Rap2. Conclusions: These results suggest that protein kinase A-dependent activation of Ral regulates cAMP-mediated exocytosis of WPB in endothelial cells. |
| Databáze: | MEDLINE |
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