title: Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway.
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.
authors.affiliation: Laboratorio de Neurofarmacología Celular, Centro de Biofísica y Bioquímica. Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 20632, Caracas, 1020-A, Venezuela. jmbrazon@gmail.com
authors.forename: Josmary
authors.initials: J
authors.lastname: Brazón
authors.forename: Craig E
authors.initials: CE
authors.lastname: Hughes
authors.forename: Jun
authors.initials: J
authors.lastname: Mori
authors.forename: Carlos
authors.initials: C
authors.lastname: Sevcik
authors.forename: Gina
authors.initials: G
authors.lastname: D'suze
authors.forename: Steve P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012604:Scorpion Venoms / Q000494:pharmacology*; D015398:Signal Transduction; D014162:Transfection; D019061:src-Family Kinases / Q000097:blood*
chemical_list: D010980:Platelet Membrane Glycoproteins; D012604:Scorpion Venoms; C098341:platelet membrane glycoprotein VI; D019061:src-Family Kinases