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Proteolysis of thrombospondin during cathepsin‐G‐induced platelet aggregation: functional role of the 165‐kDa carboxy‐terminal fragment
Author(s) -
Rabhi-Sabile Samia,
Pidard Dominique,
Lawler Jack,
Renesto Patricia,
Chignard Michel,
Legrand Chantal
Publication year - 1996
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 - 10.1016/0014-5793(96)00408-5
Subject(s) - thrombospondin , cathepsin g , chemistry , platelet , proteolysis , biochemistry , microbiology and biotechnology , cathepsin , cathepsin d , platelet activation , fibrinogen , serine , enzyme , metalloproteinase , biology , immunology
The serine‐proteinase cathepsin G (CG) is a potent agonist of platelet aggregation inducing the release and surface expression of α‐granule adhesive proteins such as fibrinogen (Fg) and thrombospondin‐1 (TSP‐1). Because Fg and TSP‐1 are potential substrates for the enzymatic activity of CG, we investigated the fate of these proteins during CG‐induced platelet aggregation using an immunoblot technique. Only a small proportion of secreted Fg was proteolyzed by CG and platelet aggregation was efficiently inhibited by anti‐fibrinogen Fab fragments. In contrast, TSP‐1 was extensively proteolyzed on aggregated platelets releasing in the milieu a fragment with M r ≈ 28 000, corresponding to the amino‐terminal heparin‐binding domain (HBD). Several antibodies, directed against the cell‐associated carboxy‐terminal TSP‐1f fragment ( M r ≈ 165 000) impaired the formation of stable macroaggregates, indicating that this fragment may contribute to platelet aggregation in the absence of the HBD.