TRANSLOCATION OF PP60C-SRC TO THE CYTOSKELETON DURING PLATELET-AGGREGATION
TRANSLOCATION OF PP60C-SRC TO THE CYTOSKELETON DURING PLATELET-AGGREGATION
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DOI：
10.1002/j.1460-2075.1992.tb05123.x
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发表时间：
1992-03-01
期刊：
影响因子：
11.4
通讯作者：
KELLIE, S
中科院分区：
文献类型：
--
作者：
HORVATH, AR;MUSZBEK, L;KELLIE, S
血小板中大量的pp 60 c-src导致推测，该激酶负责在不同激动剂激活血小板期间细胞蛋白的酪氨酸特异性磷酸化，因此涉及这些细胞的信号转导。与pp 60 v-src不同，pp 60 c-src与细胞骨架的关联似乎是转化的先决条件，pp 60 c-src在过表达c-src基因的成纤维细胞中是洗涤剂可溶的，并且其在正常细胞功能中的作用仍然难以捉摸。为了更好地了解pp 60 c-src的功能，我们研究了pp 60 c-src在血小板活化过程中的亚细胞分布及其与细胞骨架的关系。定量免疫印迹和免疫沉淀显示，pp 60 c-src是洗涤剂可溶于静息血小板，而40%的总血小板pp 60 c-src成为与血小板活化后的细胞骨架部分。我们还表明，一个小池的pp 60 c-src与膜骨架部分，在活化过程中保持不变。pp 60 c-src与细胞骨架蛋白的相互作用与聚集密切相关，并由GPIIb/IIIa受体-纤维蛋白原结合介导。我们认为pp 60 c-src易位到细胞骨架及其与细胞骨架蛋白的结合可能调节血小板酪氨酸磷酸化。
The high amount of pp60c-src in platelets has led to speculation that this kinase is responsible for tyrosine-specific phosphorylation of cellular proteins during platelet activation by different agonists, and is, therefore, implicated in signal transduction of these cells. Unlike pp60v-src, the association of which with the cytoskeleton appears to be a prerequisite for transformation, pp60c-src is detergent-soluble in fibroblasts overexpressing the c-src gene, and its role in normal cellular function remains elusive. To gain a better understanding of the function of pp60c-src we have investigated the subcellular distribution of pp60c-src and its relationship to the cytoskeleton during platelet activation. Quantitative immunoblotting and immunoprecipitation have revealed that pp60c-src is detergent-soluble in resting platelets, while 40% of total platelet pp60c-src becomes associated with the cytoskeletal fraction upon platelet activation. We have also shown that a small pool of pp60c-src is associated with the membrane skeletal fraction which remains unchanged during the activation process. The interaction of pp60c-src with cytoskeletal proteins strongly correlates with aggregation and is mediated by GPIIb/IIIa receptor-fibrinogen binding. We suggest that the translocation of pp60c-src to the cytoskeleton and its association with cytoskeletal proteins may regulate tyrosine phosphorylation in platelets.