The tyrosine kinase inhibitors methyl 2,5‐dihydroxycinnamate and genistein reduce thrombin‐evoked tyrosine phosphorylation and Ca2+ entry in human platelets

FEBS Letters

Farndale, Richard W.²  Sage, Stewart O.¹  Sargeant, Paul¹ 

[1] The Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK;Department of Biochemistry, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK

关键词: Thrombin;    Tyrosine phosphorylation;    Ca2+;    Tyrosine kinase inhibitor;    Fura-2;    Platelet;    [Ca2+]i;    cytosolic calcium concentration;    EGTA;    ethylene glycol-O;    O'-bis(2-aminoethyl)-N;    N;    N';    N'-tetraacetic acid;    SH2;    src homology region.;   

DOI  :  10.1016/0014-5793(93)81172-V

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Ca²⁺ signal generation in fura-2-loaded human platelets. Both compounds inhibited thrombin-evoked tyrosine phosphorylation and reduced the elevation of [Ca²⁺], in the presence, but not the absence, of external Ca²⁺. This suggested a selective inhibition of thrombin-evoked Ca²⁺ entry but not release from internal stores. Both compounds also reduced thrombin-evoked Mn²⁺ entry. In contrast, selective blockade of protein kinase C with Ro 31/8220-002 potentiated the thrombin-evoked Ca²⁺ signal. These data are compatible with a role for protein tyrosine phosphorylation contributing to thrombin-evoked Ca²⁺ entry in human platelets.

【 授权许可】

Unknown