Structure - function analysis of factor VII activating protease (FSAP): Sequence determinants for heparin binding and cellular functions |
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Authors: | Lars Muhl Klaus T. Preissner Sandip M. Kanse |
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Affiliation: | a Institute for Biochemistry, Medical School, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany b CSL Behring, Marburg, Germany |
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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 ΔEGF-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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Keywords: | FSAP Marburg I EGF domain Heparin Over-expression Protease activation |
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