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Laing, Gavin, Compton, S. J., Ramachandran, R., Fuller, G. L. J., Wilkinson, M. C., Wagstaff, Simon 
ORCID: https://orcid.org/0000-0003-0577-5537, Watson, S. P., Kamiguti, A. S., Theakston, R.David G. and Senis, Y. A.
(2005)
'Characterization of a novel protein from Proatheris superciliaris venom: Proatherocytin, a 34-kDa platelet receptor PAR1 agonist'. Toxicon, Vol 46, Issue 5, pp. 490-499.
Abstract
Many toxins from viperid venoms have been characterised as powerful activators of platelets. Here, the venom from the East African Lowland viper, Proatheris superciliaris, was investigated for its effect on platelets and the coagulation system. Whole P. superciliaris venom stimulated platelet shape change and aggregation; however, the stimulation of platelet activation was unaffected by the structurally distinct Src family kinase inhibitors PP1 and PD0173952, suggesting that platelet activation was mediated by a G protein-coupled receptor. A platelet reactive 34-kDa protein was isolated from P. superciliaris venom which we have designated proatherocytin. This protein induced Src kinase-independent aggregation of both human and mouse platelets that was inhibited by the serine protease inhibitor AEBSF. Proatherocytin did not clot bovine or human fibrinogen, degrade fibrinogen or hydrolyse the serine protease substrate benzoyl-FVR-pNA. It activated human PARI on stably transfected rat kidney epithelial cells, whereas no activation of the trypsin receptor PAR2 was shown. Surprisingly, Edman degradation of proatherocytin revealed sequence identity with existing disintegrin-like domains of snake venom metalloproteinases. These results suggest that proatherocytin is a highly selective PARI agonist that also causes mouse platelet aggregation, probably through cleavage of PAR4. (c) 2005 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | venom proatheris superciliaris platelet aggregation thrombin par1 agonist c-type lectin bothrops-jararaca venom cysteine-rich domain snake-venoms collagen receptor glycoprotein-vi metalloproteinase jararhagin activated receptors gene family aggregation |
| Subjects: | WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles |
| Faculty: Department: | Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group |
| Digital Object Identifer (DOI): | https://doi.org/10.1016/j.toxicon.2005.06.011 |
| Depositing User: | Ms Julia Martin |
| Date Deposited: | 30 Aug 2011 15:17 |
| Last Modified: | 17 Sep 2019 13:32 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/1962 |
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