Project Details
Projekt
Tissue Factor and PAR2 signaling in the endothelium
Applicant
Dr. Andrea Rothmeier
Subject Area
Cell Biology
Term
from 2009 to 2011
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 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 Programme
Research Fellowships
International Connection
USA
