Role of tyrosine Kinase in platelet inositol phospholipid metabolism

研究了酪氨酸激酶抑制剂染料木素对血小板功能的影响。染料木素通过降低三磷酸肌醇的产生抑制血小板胞内钙动员。发现作用位点在PI(4) p5激酶，该激酶催化PI(4,5)P2的形成。然而，染料木素似乎对凝血酶诱导的酪氨酸磷酸化没有影响，这表明染料木素对血小板钙动员的抑制作用与酪氨酸磷酸化无关。我们筛选了抑制凝血酶诱导的蛋白酪氨酸磷酸化的药物，发现staurosporine是一种蛋白激酶C抑制剂，是一种有效的酪氨酸激酶抑制剂。抑制PI(3,4)P2的形成，提示酪氨酸激酶活性与PI 3激酶密切相关。staurosporine几乎完全抑制了小麦胚芽凝集素诱导的血小板功能的各个方面，而特异性蛋白激酶C抑制剂则没有作用。这些结果表明，小麦胚芽凝集素诱导的血小板活化与酪氨酸磷酸化密切相关。

The effect of genistein, a tyrosine kinase inhibitor, was evaluated on platelet function. Genistein inhibited platelet intracellular calcium mobilization by lowering the production of inositol trisphosphate. The site of action was found to be at PI(4)P 5-kinase which catalyzes the formation of PI(4,5)P2. However, genistein appears to have no effect on tyrosine phosphorylation induced by thrombin, suggesting that the inhibitory effect of genistein on platelet calcium mobilization was independent of tyrosine phosphorylation. We screened for agents that suppress protein tyrosine phosphorylation induced by thrombin, and found that staurosporine, a protein kinase C inhibitor, was a potent inhibitor of tyrosine kinase. It inhibited the formation of PI(3,4)P2, suggesting that the tyrosine kinase activity is closely related to PI 3-kinase. Various aspects of platelet function induced by wheat germ agglutinin were almost completely inhibited by staurosporine, whereas specific protein kinase C inhibitors were without effect. These findings suggest that platelet activation induced by wheat germ agglutinin is closely related to tyrosine phosphorylation.