We have compared the effect of three legume lectins wheat germ agglutinin (WGA), Phaseolus vulgaris agglutinin (PHA) and Lens culinaris agglutinin (LCA) on function of human platelets. We have found that WGA is more active than PHA in stimulating platelet activation/aggregation, while LCA has no effect. Studies on the mechanisms involved put in evidence that WGA and PHA induce phosphorylation/activation of PLCγ2 and increase [Ca2+]i. For the first time it has been shown that Src/Syk pathway, the adapter protein SLP-76 and the exchange protein VAV participate in the PLCγ2 activation by these lectins. Moreover WGA and PHA stimulate PI3K/AKT pathway. PI3K, through its product phosphatidylinositol-3,4,5-trisphosphate activates Bruton's tyrosine kinase (BTK) and contributes to PLCγ2 activation. In conclusion, our findings suggest that PLCγ2 activation induced by WGA and PHA is regulated by Src/Syk and by PI3K/BTK pathways through their concerted action.
The molecular mechanisms involved in lectin-induced human platelet aggregation
SIGNORELLO, MARIA GRAZIA;LEONCINI, GIULIANA
2017-01-01
Abstract
We have compared the effect of three legume lectins wheat germ agglutinin (WGA), Phaseolus vulgaris agglutinin (PHA) and Lens culinaris agglutinin (LCA) on function of human platelets. We have found that WGA is more active than PHA in stimulating platelet activation/aggregation, while LCA has no effect. Studies on the mechanisms involved put in evidence that WGA and PHA induce phosphorylation/activation of PLCγ2 and increase [Ca2+]i. For the first time it has been shown that Src/Syk pathway, the adapter protein SLP-76 and the exchange protein VAV participate in the PLCγ2 activation by these lectins. Moreover WGA and PHA stimulate PI3K/AKT pathway. PI3K, through its product phosphatidylinositol-3,4,5-trisphosphate activates Bruton's tyrosine kinase (BTK) and contributes to PLCγ2 activation. In conclusion, our findings suggest that PLCγ2 activation induced by WGA and PHA is regulated by Src/Syk and by PI3K/BTK pathways through their concerted action.File | Dimensione | Formato | |
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