Generation of Gla-domainless FVIIa by cathepsin G-mediated cleavage.
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.
Nicolaisen
E M
EM
Novo Nordisk, Bagsvaerd, Denmark.
Petersen
L C
LC
Thim
L
L
Jacobsen
J K
JK
Christensen
M
M
Hedner
U
U
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
D015055:1-Carboxyglutamic Acid; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D015942:Factor VIIa