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Structure – function analysis of factor VII activating protease (FSAP): Sequence determinants for heparin binding and cellular functions
Author(s) -
Muhl Lars,
Hersemeyer Karin,
Preissner Klaus T.,
Weimer Thomas,
Kanse Sandip M.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.05.012
Subject(s) - protease , factor vii , mutant , recombinant dna , proteases , biology , microbiology and biotechnology , hek 293 cells , biochemistry , enzyme , viability assay , chemistry , cell , receptor , gene , coagulation , psychology , psychiatry
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.