Role of platelet membrane glycoprotein IIb-IIIa in agonist-induced tyrosine phosphorylation of platelet proteins.

Role of platelet membrane glycoprotein IIb-IIIa in agonist-induced tyrosine phosphorylation of platelet proteins.
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DOI:
10.1083/jcb.111.6.3117
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发表时间:
1990-12
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Shattil SJ
Shattil SJ
中科院分区:
其他
文献类型:
--
作者:
Golden A;Brugge JS;Shattil SJ

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以前用凝血酶处理血小板显示出诱导几种血小板蛋白酪氨酸磷酸化的快速变化。在这份报告中,我们表明,各种激动剂诱导血小板聚集也刺激酪氨酸磷酸化的三个蛋白质的表观分子量为84,95,和97 kD。由于血小板聚集需要激动剂诱导的整合素受体(GP IIb-IIIa)的活化以及纤维蛋白原与该受体的结合,我们研究了酪氨酸磷酸化与GP IIb-IIIa功能之间的关系。当在排除GP IIb-IIIa活化(预先在37 ℃下用EGTA破坏复合物)或纤维蛋白原结合(加入RGDS或抑制性mAb)的条件下检查血小板时,未观察到84-、95-和97-kD蛋白的酪氨酸磷酸化。然而,尽管GP IIb-IIIa活化和纤维蛋白原结合都是酪氨酸磷酸化所必需的,但它们是不够的,因为磷酸化仅在活化的血小板被搅拌并允许聚集的条件下观察到。相反,酪氨酸磷酸化不依赖于另一个主要的血小板反应,致密颗粒分泌。此外,颗粒分泌不需要这组蛋白质的酪氨酸磷酸化。这些实验证明激动剂诱导的酪氨酸磷酸化与GP IIb-IIIa介导的血小板聚集过程有关。因此,与血小板聚集相关的事件或聚集后的事件可能需要酪氨酸磷酸化。
Treatment of platelets with thrombin was shown previously to induce rapid changes in tyrosine phosphorylation of several platelet proteins. In this report, we demonstrate that a variety of agonists which induce platelet aggregation also stimulate tyrosine phosphorylation of three proteins with apparent molecular masses of 84, 95, and 97 kD. Since platelet aggregation requires the agonist-induced activation of an integrin receptor (GP IIb-IIIa) as well as the binding of fibrinogen to this receptor, we examined the relationship between tyrosine phosphorylation and the function of GP IIb-IIIa. When platelets were examined under conditions that either precluded the activation of GP IIb-IIIa (prior disruption of the complex by EGTA at 37 degrees C) or the binding of fibrinogen (addition of RGDS or an inhibitory mAb), tyrosine phosphorylation of the 84-, 95-, and 97-kD proteins was not observed. However, although both GP IIb-IIIa activation and fibrinogen binding were necessary for tyrosine phosphorylation, they were not sufficient since phosphorylation was observed only under conditions in which the activated platelets were stirred and allowed to aggregate. In contrast, tyrosine phosphorylation was not dependent on another major platelet response, dense granule secretion. Furthermore, granule secretion did not require tyrosine phosphorylation of this set of proteins. These experiments demonstrate that agonist-induced tyrosine phosphorylation is linked to the process of GP IIb-IIIa-mediated platelet aggregation. Thus, tyrosine phosphorylation may be required for events associated with platelet aggregation or for events that follow aggregation.
DOI: 10.1073/pnas.83.4.852
发表时间: 1986-02-01
影响因子: 11.1
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