Structure-function analysis of factor VII activating protease (FSAP): sequence determinants for heparin binding and cellular functions
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Published on: June 3, 2014
Lars Muhl1, Karin Hersemeyer, Klaus T Preissner
1Institute for Biochemistry, Medical School, Justus-Liebig-University Giessen, Giessen, Germany.
Abstract:
Factor VII activating protease (FSAP) is associated with cardiovascular diseases and liver fibrosis. To understand the regulation of its proteolytic activity we have characterized recombinant FSAP-mutants over-expressed in HEK-293 cells. The secreted FSAP-protein concentration correlated inversely with the enzymatic activity of the FSAP-mutants. Over-expression of enzymatically active FSAP decreased cell viability, whereas inactive variants were expressed and secreted in adequate amounts. The naturally occurring G534E-variant exhibited reduced proteolytic activity. The DeltaEGF-3 mutant showed diminished binding to and activation by heparin. Hence, regulation of FSAP activity is dependent on its EGF-3 domain and over-expression of active variants induces cell death.
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