Tissue Factor and PAR2 signaling in the endothelium

• Antragstellerin: Dr. Andrea Rothmeier
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2009 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 134409466

Increased activity of protease activated receptor 2 (PAR2) has been associated with tumor angioge-nesis. Moreover, the inhibition of PAR2-activation, which is mediated by the binary complex of tissue factor (TF) and factor VII, dramatically reduces tumor vasculature and progression. Therefore, pro-angiogenic signaling by PAR2 seems to be of clinical relevance. The cytoplasmic domain of TF (TF-tail) plays a dual role in PAR2-signaling, inhibiting PAR2-activity, but also exerting pro-angiogenic effects when it is phosphorylated. The phosphorylation of TF-tail is exclusively promoted by PAR2 and seems to present a key event in PAR2-mediated angiogenesis. The aim of the proposed project is to elucidate the interaction of TF and PAR2 in the endothelium, in particular the role of the phosphorylation of TF-tail in PAR2-signaling. Experiments will be performed in human endothelial cells and include localization studies of TF and PAR2, the identification of the TF-tail phosphorylating kinase as well as investigations of the pro-angiogenic mechanisms of phosphorylated TF-tail. The results of this project will increase our knowledge of the complex signaling associated with TF and may further provide new targets for anti-angiogenic therapy.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeber: Professor Dr. Wolfram Ruf