Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells.

ABSTRACT: Thrombin is the key serine protease of the coagulation cascade and a potent trigger of protease-activated receptor 1 (PAR1)-mediated platelet aggregation. In recent years, PAR1 has become an appealing target for anticoagulant therapies. However, the inhibitors that have been developed so far increase bleeding risk in patients, likely because they interfere with endogenous PAR1 signaling in the endothelium. Because of its complexity, thrombin-induced signaling in endothelial cells has remained incompletely understood. Here, we have combined stable isotope amino acids in cell culture, affinity-based phosphopeptide enrichment, and high-resolution mass spectrometry and performed a time-resolved analysis of the thrombin-induced signaling in human primary endothelial cells. We identified 2224 th

SUBMITTER: van den Biggelaar M 

PROVIDER: S-EPMC3962174 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature