Interaction of viper venom serine peptidases with thrombin receptors on human platelets

FEBS Letters

Kuliopulos, Athan¹  Santos, Beatriz F.³  Serrano, Solange M.T.³  Niewiarowski, Stefan² 

[1] Tufts University School of Medicine, Boston, MA, USA;Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA;Instituto Butantan, Sao Paulo, Brazil

关键词: Thrombin receptor;    Protease activated receptor;    Platelet activation;    Viper venom protease;    Calcium mobilization;    Heparin;    Hirudin;    Thrombomodulin;   

DOI  :  10.1016/S0014-5793(00)01803-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The serine peptidases, thrombocytin and PA-BJ, isolated from the venom of Bothrops atrox and Bothrops jararaca, respectively, induce platelet aggregation and granule secretion without clotting fibrinogen. The specific platelet aggregation activity of each enzyme was about 15 times lower than that of thrombin. This activity was blocked by monoclonal antibodies recognizing protease activated receptor 1 (PAR1) and by heparin, but not by hirudin nor thrombomodulin. Both enzymes induced calcium mobilization in platelets and desensitized platelets to the action of thrombin and the SFLLRN peptide. We compared the effect of thrombin, PA-BJ, and thrombocytin on the degradation of the soluble N-terminal domain of the PAR1 receptor. The major cleavage site by thrombin and both viper enzymes was Arg41–Ser42. In addition, a rapid cleavage of the peptide bond at Arg46–Asn47 by the viper enzymes was observed, resulting in the inactivation of the tethered ligand. PA-BJ and thrombocytin both cleaved at 41–42 and 46–47 peptide bonds, and fragment 42–103 disappeared rapidly. Both viper enzymes caused calcium mobilization in fibroblasts transfected with PAR4 and desensitized these cells to the thrombin action. In conclusion, both PAR1 and PAR4 mediate the effect of viper venom serine peptidases on platelets.

【 授权许可】

Unknown