S. Rabhisabile et al., PROTEOLYSIS OF THROMBOSPONDIN DURING CATHEPSIN-G-INDUCED PLATELET-AGGREGATION - FUNCTIONAL-ROLE OF THE 165-KDA CARBOXY-TERMINAL FRAGMENT, FEBS letters, 386(1), 1996, pp. 82-86
The serine-proteinase cathepsin G (CG) is a potent agonist of platelet
aggregation inducing the release and surface expression of alpha-gran
ule adhesive proteins such as fibrinogen (Fg) and thrombospondin-l (TS
P-1), Because Fg and TSP-1 are potential substrates for the enzymatic
activity of CG, we investigated the fate of these proteins during CG-i
nduced platelet aggregation using an immunoblot technique, Only a smal
l proportion of secreted Fg was proteolyzed by CG and platelet aggrega
tion was efficiently inhibited by anti-fibrinogen Fab fragments, In co
ntrast, TSP-1 was extensively proteolyzed on aggregated platelets rele
asing in the milieu a fragment with M(r) approximate to 28 000, corres
ponding to the amino-terminal heparin-binding domain (HBD), Several an
tibodies, directed against the cell-associated carboxy-terminal TSP-lf
fragment (M(r) approximate to 165 000) impaired the formation of stab
le macroaggregates, indicating that this fragment may contribute to pl
atelet aggregation in the absence of the HBD.