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The tyrosine kinase inhibitors methyl 2,5‐dihydroxycinnamate and genistein reduce thrombin‐evoked tyrosine phosphorylation and Ca 2+ entry in human platelets
Author(s) -
Sargeant Paul,
Farndale Richard W.,
Sage Stewart O.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81172-v
Subject(s) - genistein , tyrosine , platelet , phosphorylation , tyrosine kinase , thrombin , chemistry , tyrosine phosphorylation , biochemistry , protein tyrosine phosphatase , platelet derived growth factor receptor , endocrinology , biology , medicine , signal transduction , receptor , growth factor
Platelet activation is associated with the phosphorylation of a number of platelet proteins at tyrosine residues. The significance of this is unknown. Here we have investigated the effects of two tyrosine kinase inhibitors, methyl 2,5‐dihydroxycinnamate and genistein, on thrombin‐evoked protein tyrosine phosphorylation and Ca 2+ signal generation in fura‐2‐loaded human platelets. Both compounds inhibited thrombin‐evoked tyrosine phosphorylation and reduced the elevation of [Ca 2+ ], in the presence, but not the absence, of external Ca 2+ . This suggested a selective inhibition of thrombin‐evoked Ca 2+ entry but not release from internal stores. Both compounds also reduced thrombin‐evoked Mn 2+ entry. In contrast, selective blockade of protein kinase C with Ro 31/8220‐002 potentiated the thrombin‐evoked Ca 2+ signal. These data are compatible with a role for protein tyrosine phosphorylation contributing to thrombin‐evoked Ca 2+ entry in human platelets.