title: Generation of Gla-domainless FVIIa by cathepsin G-mediated cleavage.
abstract: Coagulation factor VII contains ten gamma-carboxyglutamic acid residues in the N-terminal region (Gla-domain) which are essential for the hemostatic function of FVII. The present study shows that granulocyte cathepsin G degrades the Gla-domain of FVIIa in vitro. Characterization of the truncated FVIIa by SDS-PAGE and N-terminal amino acid sequence analysis revealed that cleavage had occurred between Tyr-44 and Ser-45 and that further cleavage was only obtained on extensive cathepsin G exposure. Cleavage of vitamin K-dependent coagulation factors by cathepsin G may play a role in vivo, and it offers a convenient way of obtaining proteins deprived of their Gla-domain for functional and structural studies.
authors.affiliation: Novo Nordisk, Bagsvaerd, Denmark.
authors.forename: E M
authors.initials: EM
authors.lastname: Nicolaisen
authors.forename: L C
authors.initials: LC
authors.lastname: Petersen
authors.forename: L
authors.initials: L
authors.lastname: Thim
authors.forename: J K
authors.initials: JK
authors.lastname: Jacobsen
authors.forename: M
authors.initials: M
authors.lastname: Christensen
authors.forename: U
authors.initials: U
authors.lastname: Hedner
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001777:Blood Coagulation; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D015942:Factor VIIa / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007525:Isoelectric Focusing; D008969:Molecular Sequence Data; D011817:Rabbits; D012697:Serine Endopeptidases
chemical_list: D015055:1-Carboxyglutamic Acid; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D015942:Factor VIIa