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PMID:21322750

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Citation

Brazón, J, Hughes, CE, Mori, J, Sevcik, C, D'suze, G and Watson, SP (2011) Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway. Platelets 22:165-72

Abstract

In humans and other mammals, Tityus discrepans (Td) scorpion envenomation produces a variety of systemic effects including respiratory distress, a generalized inflammatory reaction, modulation of blood pressure, fibrin formation, and platelet activation. For many of these effects, the venom components and underlying mechanisms are not known. In the present study, we demonstrate that Td venom (TdV) stimulates integrin αIIbβ3-dependent aggregation of washed human and mouse platelets downstream of Src kinase activation. The pattern of increase in tyrosine phosphorylation induced by TdV in human platelets is similar to that induced by the collagen receptor GPVI, and includes FcR γ-chain, Syk, and PLC γ 2. Confirmation of GPVI activation by TdV was achieved by expression of human GPVI in chicken DT40 B cells and use of a reporter assay. To our surprise, TdV was able to activate mouse platelets deficient in the GPVI-FcR γ-chain complex through a pathway that was also dependent on Src kinases. TdV therefore activates platelets through GPVI and a second, as yet unidentified Src kinase-dependent pathway.

Links

PubMed Online version:10.3109/09537104.2010.544343

Keywords

Animals; Blood Platelets/drug effects; Blood Platelets/metabolism; Cells, Cultured; Chickens; Humans; Mice; Mice, Inbred C57BL; Platelet Activation/drug effects; Platelet Membrane Glycoproteins/deficiency; Platelet Membrane Glycoproteins/genetics; Platelet Membrane Glycoproteins/metabolism; Scorpion Venoms/pharmacology; Signal Transduction; Transfection; src-Family Kinases/blood

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

TITDI:KA156

involved_in

GO:0044477: envenomation resulting in negative regulation of platelet aggregation in other organism

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

TITDI:KA156

GO:0044477: envenomation resulting in negative regulation of platelet aggregation in other organism

ECO:0000314:

P

Fig 2

complete
CACAO 6559


See also

References

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