Non-proteolytic activation of cellular protransglutaminase (placenta macrophage factor XIII).
Plasma Factor XIII is a zymogen (plasma protransglutaminase) with the tetrametric structure A2B2, whereas the cellular protransglutaminase, i.e. Factor XIII in the platelet and monocyte/macrophage, consists exclusively of A subunits (A2). It is generally accepted that at Ca2+ concentrations comparable with that in plasma the proteolytic removal of an N-terminal activation peptide is the prerequisite for the Ca2(+)-induced formation of a catalytically active configuration of subunit A. In this study it was demonstrated that at high concentrations NaCl or KCl induced a non-proteolytic activation of cellular (placental macrophage) but not plasma protransglutaminase. The activation depended on time and salt concentration, and Ca2+, in the range 0-20 mM, greatly enhanced the activation process. At 1.25 M-NaCl maximal activation occurred within 60 min in the presence of 2 mM-CaCl2, and even at physiological NaCl concentration a slow progressive activation could be observed in the presence of Ca2+. The specific activity of salt-activated Factor XIII was 1.5-2.0-fold higher than that obtained after thrombin activation. The non-proteolytic activation of cellular protransglutaminase was abolished by the addition of subunit B of plasma Factor XIII in stoichiometric amount, which suggests that (one of) the physiological function(s) of the B subunit in plasma Factor XIII is to prevent the slow spontaneous activation of A subunit that would occur in a plasmatic environment.
Polgár
J
J
Department of Clinical Chemistry, University School of Medicine, Debrecen, Hungary.
Hidasi
V
V
Muszbek
L
L
D002118:Calcium / Q000494:pharmacology; D004789:Enzyme Activation; D005176:Factor XIII / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000201:enzymology; D009994:Osmolar Concentration; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012965:Sodium Chloride / Q000494:pharmacology; D011503:Transglutaminases / Q000378:metabolism*
D012965:Sodium Chloride; D005176:Factor XIII; D011503:Transglutaminases; D002118:Calcium